cytokine

Psoriasis is a chronic skin disease that usually manifests as white and silver spots on the skin. Because of its anti-inflammatory properties, we investigated the effects of ivermectin (IVM) on imiquimod (IMQ)-induced psoriasis in rats. Fifteen rats were assigned to 3 different groups (n=5 per group): the control group received normal water and food; the psoriasis group, in which psoriasis was induced by topical application of IMQ (1 mg per rat), and treatment group where rats were treated daily with topical IVM-gel (1%) from day 3 to 7. The Psoriasis Area Severity Index (PASI) Score for the entire treatment period was used to assess erythema, silver scale, and skin thickness on the dorsal region of rats, and the spleen-to-body weight index on day 7 was examined. Moreover, histological assessment of skin tissues was performed using fluorescence immunostaining and hematoxylin-eosin (H&E) staining.  The severity of lesions in the ivermectin group was reduced compared to the IMQ group, with a significant decrease in the average PASI scores. The results of fluorescence immunostaining showed that topical administration of IVM-gel reduced inflammation by decreasing Toll-like receptor 4 (TLR4) levels and p65 nuclear factor kappa-B (NF-κB). Furthermore, findings from H&E staining revealed that IVM-gel decreased dermal fibrosis, epidermal thickness, and infiltration of inflammatory cells caused by IMQ.  Based on the obtained results, it can be concluded that IVM-gel can effectively reduce psoriasis lesions due to its therapeutic properties, such as anti-inflammatory effects via targeting TLR4/p65 NF-κB.

Cerebral ischemia/reperfusion (I/R) injury is the most prevalent form of brain stroke, affecting many patients worldwide. It is believed that oxidative stress and inflammation play major roles in the damage that occurs after the initiation of the disease.

Therefore, for the first time, the current study aimed to investigate the neuroprotective effects of bupropion against cerebral I/R damage in a rat model.

Forty male rats were divided into four groups: Control, cerebral I/R, and two diseased groups that received 60 and 100 mg/kg of bupropion. One day after induction of the disease, behavioral tests, including grid walking, novel object recognition, and modified neurological severity score (mNSS), were performed on the rats. The levels of inflammatory cytokines, including IL-1β, TNF-α, IL-6, and IL-10, were measured in the rats' brain homogenates. Additionally, the levels of MDA, catalase (CAT), superoxide dismutase (SOD), reduced glutathione (GSH), and NO2 - were measured.

Bupropion administration was associated with improved performance in the novel object recognition and grid walking behavioral tests, as well as in the neurological disorder scores, in cerebral I/R rats. Moreover, BCAAO-induced inflammation was reduced by the administration of this drug, evidenced by reduced levels of cytokines IL-1β, TNF-α, and IL-6 and upregulation of IL-10. Additionally, membrane lipid peroxidation was reduced in the cerebral I/R rats receiving 100 mg/kg bupropion, and the level of SOD activity was improved in these animals. Finally, the administration of bupropion prevented the increase in NO2 - levels induced by BCAAO.

In conclusion, bupropion has neuroprotective effects against cerebral I/R damage by reducing inflammation and oxidative stress in the brain.

Malaria parasites have gradually developed resistance to commonly used antimalarial drugs. For decades, chloroquine was the most widely used drug to eradicate malaria. However, with the spread of chloroquine resistance, many countries have adopted combination therapies that utilize two drugs acting synergistically instead of monotherapy. In this study, the synergistic effect of chloroquine and the semipolar extract of Artemisia kopetdaghensis. Semipolar extract (SPE) was investigated in vivo through pathological and parasitological studies on mouse model.

Sixty female Balb/c mice infected with the Plasmodium berghei (P. berghei) parasite were treated with different concentrations of the semipolar extract of Artemisia kopetdaghensis (SPE) according to the protocol. The mean percentage of parasitemia, the mean survival time of the mice, the serum levels of IFN-γ, IL-4, IL-17, and TGF-β, and the effects of the SPE on the kidney, spleen, and liver tissues were investigated and compared across different treatment groups. The data were analyzed using Bonferroni, ANOVA, and Tukey tests.

The semipolar extract of Artemisia kopetdaghensis (SPE) demonstrated better therapeutic effects in both synergistic and monotherapy conditions compared to chloroquine alone. The combination of chloroquine and SPE resulted in the lowest parasitemia rate, the highest percentage of parasite inhibition, and the longest average survival time. Pathological studies showed no signs of acute toxicity in the organs.

This study demonstrated that using chloroquine in combination with Artemisia kopetdaghensis semipolar extract has synergistic effects in reducing parasitemia, enhancing the inhibitory effect on parasite growth and reproduction, and balancing the host immune system.

Breast cancer is the most prevalent malignancy among women. Inflammatory cytokines such as tumor necrosis factor-α (TNF-α) play a critical role in cancer pathogenesis and malignancy.

This study aimed to evaluate serum levels of TNF-α across different subtypes and stages of breast cancer.

Serum samples were collected from 114 patients with various subtypes and stages of breast cancer. Tumor necrosis factor-α levels were measured using enzyme-linked immunosorbent assay (ELISA).

Serum TNF-α levels were significantly higher in patients with triple-negative breast cancer (TNBC) compared to those with other breast cancer subtypes (P < 0.0001). Additionally, TNF-α levels were markedly higher in patients with stage III carcinoma than in those with stages I and II (P < 0.0001). Among stage III TNBC patients, TNF-α concentrations were significantly higher than those in stage III patients from other groups (P < 0.05).

Evaluating serum TNF-α concentrations can provide valuable insights for estimating cancer prognosis and guiding patient management.

CD8+ T cells have been found to accumulate in atherosclerotic plaques. However, the specific role of CD8+ T cell subsets in the development of atherosclerosis is still not fully understood. To investigate the presence and functions of type 1 CD8+ T (Tc1) cells and interleukin-17 (IL-17)-producing CD8+ T (Tc17) cells. Apolipoprotein E-deficient mice were fed a high-fat diet to induce atherosclerosis. Flow cytometry was used to identify and isolate aortic CD8+ T cell subsets, which were then cultured in vitro to assess their pro-inflammatory activities. The cholesterol content of the CD8+ T cell subsets was quantified. T-box expressed in T cells (T-bet)+ Tc1 cells and retinoic acid-related orphan receptor gamma t (RORγt)+ Tc17 cells were found in the atherosclerotic aorta. Aortic CD8+ T cells showed lower pro-inflammatory activity compared to splenic counterparts, with less interferon-gamma (IFN-γ) (P <0.01) and tumor necrosis factor-alpha (TNF-α) production (P <0.01). Surprisingly, aortic CD8+ T cells expressed little IL-17 and interleukin-21 (IL-21) despite the presence of Tc17 cells. Aortic Tc1 and Tc17 cells expressed high levels of 2B4 and programmed cell death protein 1 (PD-1). Furthermore, aortic Tc1 and Tc17 cells had higher cholesterol contents than splenic CD8+ T cells (P <0.05, respectively). Cholesterol treatment decreased IFN-γ expression in Tc1 cells (P <0.001) and reduced IL-17 expression in Tc17 cells (P <0.001). Additionally, cholesterol up-regulated 2B4 and PD-1 on Tc1 (P <0.001) and Tc17 cells (P <0.001). Aortic CD8+ T cells, particularly aortic Tc17 cells, are functionally exhausted in atherosclerosis, possibly due to the influence of cholesterol.

Breast cancer is the leading cause of cancer-related deaths in women. Cytokines have been linked to various cancers, and both benign and malignant breast diseases are associated with inflammation. However, there is limited understanding of how the immune system's cytokine response varies among different subtypes of breast cancer. To assess cytokine levels in breast cancer patients according to their subtypes and investigate the potential role of these cytokines in treatment. Patients with stage 1-2 breast cancer and healthy volunteers were included in the study. The breast cancer patients were classified as luminal A, luminal B, and triple negative based on ER, PR, HER2 receptor status, and Ki67 score of trucut biopsy results. Multiplex assay and flow cytometry were used to quantify the concentrations of IL-1β, IFN-α2, IFN-γ, TNF-α, MCP-1, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, IL-23, and IL-33 in serum samples collected from all participants.  Age, menopausal status, and hematologic parameters were also compared between groups. The study involved 19 luminal A, 20 luminal B, 18 triple-negative patients and 21 healthy volunteers. TNF-α, IL-6, IL-8, IL-10, IL-12p (p70), IL-18, and IL-23 cytokines were significantly higher in breast cancer patients than in healthy volunteers. Significant differences in IFN-γ, IL-6, IL-8, IL-10, IL-12p (p70), IL-17A, IL-18, and IL-23 were observed between subtypes, with triple-negative patients showing lower cytokine levels, except for MCP-1. The decreased levels of cytokines in triple-negative breast cancer indicate lower immunogenicity leading to more aggressive tumor progression as a result of an insufficient immune response.

Rosemary (Ros) is a member of the Lamiaceae family known for its antitumor properties. However, its low water solubility and impaired bioavailability are limiting factors when using rosemary extract. Liposomes are synthetic vesicles that offer permeability, improved bioavailability, and lack of immunogenicity and toxicity, making them ideal for delivering various drugs.

To prepare liposomes (HSPC/Chol/mPEG2000-DSPE) containing rosemary alcoholic extract (LipRos) and evaluate its antitumor properties in a mouse model of colorectal cancer (CRC).

LipRos were prepared and characterized. CRC was induced in Balb/c mice by subcutaneous injection of C26 cells, and tumor size was monitored continuously. The MTT assay was performed to evaluate cytotoxicity, and liver and kidney function tests were conducted to assess safety. The expression of the pro-apoptotic gene B-cell-lymphoma-2 (Bcl-2), the anti-apoptotic gene Bcl-2-associated-X-protein (Bax), and the expression of cytokines Tumor-necrosis-factor-alpha (TNF-α), Transforming-growth-factor-beta (TGF-β), and Interferon-gamma (IFN-γ) were investigated using real-time PCR. Flow cytometry was used to evaluate the count of cytotoxic (CTL) and regulatory T lymphocytes (Tregs) in spleen and tumor tissue.

The results showed that the size of liposomal formulations and their encapsulation efficiency were 113.4 nm and 85%, respectively. The MTT assay demonstrated insignificant cytotoxicity of LipRos on splenocytes, and the tumor size was significantly reduced in the LipRos group (P=0.00045). LipRos also significantly decreased Bcl-2 gene expression (P=0.0086), increased Bax and IFN-γ gene expression (P=0.031), and enhanced the infiltration of CTLs in tumor tissue (P=0.023).

This study showed that PEGylated (Poly-Ethylene-Glycol) liposomes containing rosemary extract exhibit an antitumor effect on C26 colorectal cancer cells through multiple mechanisms. These findings can be utilized in future studies.

The main goal in cancer treatment is to eliminate tumor cells with minimal harm to healthy tissue. The immune system is ideal for this task as it can identify and eliminate abnormal cells while providing long-term defense against recurrence. Various immune-based cancer treatments activate the immune system or help cancer cells recognize and activate immune cells within the tumor. Immunoregulatory cytokines play a crucial role in treating immune disorders. They regulate macrophage degradation of antigens and promote cellular functions. Lymphocyte interactions can lead to immune cell maturation, while other products limit lymphocyte activation. Cytokines are categorized as interleukins, growth factors, interferons, and colony-stimulating factors. Soluble proteins known as cytokines are essential for mediating and regulating cell interactions in various parts of the body, including the nervous system, gut, and bone remodeling. The study of cytokines’ structure and function has proven incredibly beneficial for both immunology and commercial research. By understanding the different domains and analogues of cytokines, researchers have gained important knowledge about how these proteins bind to receptors. Moreover, identifying similarities between various cytokines has offered valuable insights into the workings of cytokine receptors. Understanding the mechanisms behind immunotherapy resistance is important to identify new therapeutic targets. By investigating these pathways, researchers can develop innovative strategies to overcome resistance and improve treatment outcomes. Combining therapeutic modalities to target multiple aspects of the tumor microenvironment simultaneously can overcome the limitations of individual treatments and improve antitumor response. Understanding resistance mechanisms to immunotherapies can lead to the development of tailored strategies to combat treatment resistance and maximize treatment response.

Investigating the impacts of plant-based substances on the regulation of pro-inflammatory M1 and anti-inflammatory M2 cytokines could have significant implications for immune-related health conditions. Seven Persicaria plant species from sub-Saharan Africa were specifically selected for analysis, based on their traditional use in treating inflammation. To investigate the inhibitory effects of methanol leaf extracts from selected plants on enzymes involved in chronic inflammation. The inhibition of nitric oxide production, acetylcholinesterase activity, and 15-lipoxygenase activity was assessed using the Griess reagent method, Ellman’s colorimetric method, and the ferrous oxidation-xylenol orange assay. The quantity of M1/M2 cytokines released was quantified using a flow cytometer At a concentration of 50 µg/mL, the methanol extracts of P. limbata exhibited the highest NO inhibition (97.67%), followed by P. nepalensis (93.06%) and P. setosula (92.78%). The NO inhibition caused by the plant extracts was correlated directly with the decrease in NO release by the LPS-stimulated macrophages. Furthermore, the pro-inflammatory enzyme assays indicated that the methanol extracts of P. setosula exhibited the highest enzyme inhibitory activity (LOX 89.59%, AChE 72.12 %). This was followed by P. limbata (with 92.76% for LOX and 56.93% for AChE) and P. nepalensis (with 88.16% for LOX and 47.17% for AChE). Cytokine assays revealed that the extracts of P. limbata had significant dose-dependent suppressive effects on IFN-γ and TNF-α expression while promoting the secretion of IL-2, IL-4, IL-6, and IL-10. Extracts of P. limbata contain immunomodulatory compounds that could be further explored as potential remedies to target the molecular drivers of chronic inflammation.

Cytokines are important in many pathobiological processes of chronic obstructive pulmonary disease (COPD). This study aimed to determine the relationship between serum levels of interleukin-33 (IL- 33) and the severity of COPD disease.

In this cross-sectional research, the study population consisted of all COPD patients referring to the pulmonary clinic of Imam-Ali Hospital of Zahedan city. Sixty patients were selected using the available sampling method. Serum IL-33 levels were measured by the quantitative ELISA method.

Of 60 patients, 23 (38.3%) and 37 (61.7%) subjects were male and female, respectively. Analysis shows a significant difference between serum IL-33 of the two groups with regard to the severity of COPD disease. There was a statistically significant negative relationship between the serum level of IL-33 and the severity (decrease of forced expiratory volume in one second (FEV1)) of COPD disease.

Our results indicate a systemic release of IL-33 correlated with the severity of COPD.

The endometriosis treatment was critical due to complications associated with current drug delivery system. The present study was conducted with aim to compare the curative effect of Vitamin D3 (VTD3) and Omega–3 (OG3) with Diphereline during the treatment of endometriosis.

In this study, endometriosis was induced in different groups containing 60 adult female rats. The rat model was categorized into 6 groups untreated and treated (Olive Oil (solvent), VTD3 (42 mcg/kg/day), OG3 (450 mg/kg/day), VTD3+OG3, Diphereline (3 mg/kg/day)). The suspension containing combination of Diphereline and supplements was injected and treated for 4 weeks to analyze the effect of supplements. The interleukin -6 (IL-6) and Tumor necrosis factor – alpha (TNFα) inflammatory responses were measured from the serum samples while endometrial implants was dissected and histopathological investigation was done.

At the end of four weeks, pathologic score decreased significantly with simultaneous measurement of inflammation score of endometriotic lesion, size of implant area, IL-6, TNFα response and compared with untreated female rat. No significant different was observed in groups undergoing treatment of VTD3, OG3 and Diphereline. The combined effect of VTD3+OG3 has similar responses with Diphereline treated endometrial implants.

treatment of VTD3 deficiency and making a change in dietary habits of high-risk population for endometriosis from adolescence may also play a preventative role in adulthood.

Besides the clinical and laboratory research on the COVID-19 virus, the bioinformatics study in the field of genetics of immunity to COVID-19 is of particular importance. In this account, studies show that in patients with COVID-19, the level of tumor necrosis alpha (TNFα) and interleukin-6 (IL-6) is high and in severe cases of COVID-19, the production of IL-6, TNF-α, and other cytokines increases profoundly. On the other hand, investigating the molecular structure and receptors of IL-6 and TNFα and the structural analysis of the receptor proteins may potentially help to develop new therapeutic plans for COVID-19 infection.

To identify genes with significant and different expressions in patients with COVID-19 in a microarray data set containing transcriptional profiles from GEO as a functional genomic database the GEO query package version 2.64.2 in a programming language R version 4.2.1 was downloaded. In this way, functional enrichment analysis for DEGs, WikiPathways, REGO, gene ontology, and STRING database was also investigated and employed.

The structure and function of pro-inflammatory cytokines TNFα and IL-6 involved in the pathogenesis of COVID-19 were investigated, and in general, after performing various analyses in this study and extracting A series of genes with different expressions from the KEGG database, the final 5 DEGs include CXCL14, CXCL6, CCL8, CXCR1, TNFRSF10, and the relationship and expression effects of them were observed in different pathways.

IL-6 and TNFα were involved in immunological processes that had a direct and indirect relationship with the activation of cytokines, including IL6 and TNF-a, and cytokine storm, and this indicates their role in the formation of problems and complications, including ARDS, in COVID-19 patients. Of course, determining the effectiveness of each of these genes requires more specialized and clinical studies.

Ulcerative colitis (UC) is an inflammatory bowel disease that leads to gastrointestinal ulcers. An overactive immune response against the intestinal microbiota has been suggested as one of the pathogenic factors. Some evidence indicates the immunomodulatory effects of Bifidobacterium lactis. sugarcane molasses, rich in vitamins and nutrients, can be used to compensate for the related nutrient deficiencies.

This study aims to evaluate the effects of sugar-free sugarcane (SFS)-molasses on the immune system of UC patients.

Bifidobacterium lactis was cultivated in MRS broth and killed by UV de-sugarization of sugarcane molasses. It was prepared using the Steffen method. Peripheral blood mononuclear cells (PBMCs) of 12 UC patients were separated by Ficoll-Hypaque centrifugation. Peripheral blood mononuclear cells, SFS-molasses, and B. lactis were co-cultured. After 18h, the expression level of the FOXP3 gene was assessed by RT-qPCR (real-time PCR). The interferon gamma (IFN-γ) and transforming growth factor beta (TGF-β) were measured in the supernatant of PBMCs by ELISA.

Transforming growth factor beta in the SFS-molasses group was significantly increased compared to the controls (P = 0.032). The TGF-β in SFS-molasses + bacteria and the bacteria-alone groups increased compared to the control group (P = 0.039 and P = 0.049, respectively). The level of IFN-γ in the SFS-molasses group was significantly decreased compared to the controls (P = 0.004). Interferon gamma increased in the SFS-molasses + B. lactis group compared to the controls, but this was not significant. Expression of FOXP3 wasn’t affected after SFS-molasses treatment.

These data showed that SFS molasses increases the levels of anti-inflammatory cytokine TGF-β and decreases the pro-inflammatory cytokine IFN-γ levels. These results may encourage researchers to continue studying the possible application of molasses as a nutritious food for patients with UC.

Pancreatic cancer commonly refers to Pancreatic Ductal Adenocarcinoma (PDAC) which accounts for more than 90% of pancreatic cancers (1). The substantial burden of disease is characterized by the approximate deaths of as many as cases annually. PDAC as the seventh leading cause of cancer-induced mortalities globally, has been a focal point of research in the field of oncology (2).Despite the vast research and significant effort devoted to the treatment of PDAC, the 5-year survival rate for this cancer remained less than 5%. This scant survival rate is a consequence of late-onset diagnosis, accelerated tumor growth, and limited extant treatments. Hence, innovative strategies, such as immunotherapy, seek to enhance antitumor immune reactions, offering a more precise and targeted therapeutic alternative (1).Immunotherapy is categorically segmented into four primary subtypes: vaccines, cellular therapies, cytokines, and antibodies, with Immune Checkpoint Inhibitors (ICIs) falling under the latter classification (3).Cancer vaccines stimulate immune responses by leveraging tumor-associated antigens to activate cytotoxic T-lymphocytes. These antigens can be sourced from whole-cell tumor lysates, recombinant tumor peptides, or recombinant viruses (1). Regarding vaccines, messenger RNA (mRNA) vaccines have been more promising than conventional vaccines, which present various challenges, for a personalized therapeutic approach in pancreatic cancer. These vaccines utilize the genetic profile of an individual’s tumors, particularly those with mutant Kras, and custom proteins can be encoded (3). KRAS as a proto-oncogene has been recognized as mutated among 90% of patients diagnosed with PDAC, making it a valid target. They enhance antitumor immunity against oncogenic KRAS by presenting oncogenic KRAS neoantigens to major histocompatibility complex molecules, leading to the generation of cancer-specific memory T cells with long-term efficacy. In terms of other vaccines that are under investigation regarding their efficacy in PDAC, telomerase vaccines, gastrin vaccines, survivin-targeting vaccines, heat-shock protein peptide complex-based vaccines, MUC-1 targeting vaccines, listeria-based vaccines, dendritic cell-based vaccines, Granulocyte-Macrophage Colony-Stimulating Factor (GMCSF)-allogeneic pancreatic tumor cells (GVAX) vaccines, and Hyper-Acute-Pancreas algenpantucel-L (HAPa), Mucin-1 (MUC-1) vaccines can be mentioned (4–6).Adoptive cell therapy is a rapidly growing technology consisting of NK cells or T cells that are either allogeneic or autologous. and have been genetically modified to target specific proteins using chimeric antigen receptors and T-cell receptors. These engineered cells are designed to recognize a peptide/MHC complex to effectively eliminate cancer cells. Numerous Chimeric Antigen Receptor (CAR) T-cell therapies have been approved for the treatment of different hematological malignancies. In PDAC, mesothelin CAR-T therapy has shown promise in preclinical mouse models by extending survival. However, the translation of this strategy to clinical settings for solid tumors faces various obstacles. To address these challenges, the development of next-generation CAR-T cells is underway to enhance the effectiveness of this therapy (3,7).Cytokine therapies, including the use of Interleukin-2 (IL-2) and Interferon alpha (IFN-α), have been utilized as an early form of immunotherapy in the management of malignant conditions, establishing them as foundational components of this treatment approach. Cytokines with immune stimulatory properties, including IL-2, IL-15, GM-CSF, and IFN-α, have been incorporated as adjunctive elements in comprehensive immunotherapy strategies for PDAC. While monotherapy with cytokines showed promise during the peri-operative period, no recent studies have been published on this subject in the last ten years (3,8).ICIs are monoclonal antibodies that target specific extracellular proteins expressed by tumor cells or tumor-associated lymphocytes, leading to the suppression of the body’s immune response against the cancer (1). To address some of the main ICIs, Anti-PD-1/Anti-PD-L1, Anti-CTLA-4, Anti-TIM-3, Anti-TIGIT, and Anti-LAG-3 can be mentioned. Anti-PD-1/Anti-PD-L1 blocks the PD-1 pathway in which PD-1 ligation induces self-tolerance by preventing the activation of T cells as well as their proliferation. In PDAC, despite other solid tumors, the efficacy of Anti-PD-1/Anti-PD-L1 as monotherapy was not as promising as its effectiveness in combination with chemotherapy. The inhibitory CTLA-4 receptor on T cells competes with the co-stimulatory receptor CD28 for binding to the CD80 and CD86 ligands on antigen-presenting cells (APCs). CTLA-4 has a higher affinity for these ligands. Lower levels of CTLA-4 and higher expression of CD80 in PDAC are associated with increased survival rates. Binding of CTLA-4 primarily inhibits the activation of naïve T cells in lymphoid organs, but may also hinder the direct anti-tumor activity of T cells in the effector phase, potentially by reducing the presence of suppressive regulatory T cells. Based on a previous study, the co-administration of GVAX with anti-CTLA-4 appears to stimulate a T cell-mediated immune reaction and could potentially enhance the survival rate of patients with advanced PDAC. Numerous clinical trials are currently underway to assess the efficacy of the combination of anti-CTLA-4 therapy with other immunotherapeutic agents and/or radiotherapy in the treatment of PDAC (8). Both PD-L1 and CTLA-4 are often overexpressed in a subgroup of PDAC and are associated with poorer survival outcomes, making them potential targets for therapeutic intervention (1).In conclusion, despite the aforementioned substantial investigations regarding therapeutic approaches for PDAC, treatment of this highly impacting disease is hampered by so many obstacles. Further research is necessary to overcome the remission-disrupting factors such as immunity evasions, altered tumor microenvironment, immunosuppressive activities, etc.Conflict of InterestThe authors had no competing interests.

Investigating the ameliorative effects of melatonin on cytokine levels, apoptosis, and NF-κB immunoreactivity in rats with cerulein-induced acute pancreatitis. Thirthy-two Wistar Albino rats were divided into four groups: Control group which didn’t undergo acute pancreatitis induction and was left without treatment, pancreatitis group in which the acute pancreatitis was induced by 2 successive intraperitoneal doses of cerulein at a 2-hour interval (50 µg/kg and then 25 µg/kg), melatonin-treated pancreatitis group which was intraperitoneally administrated with 50 mg/kg of melatonin, 30 min before each cerulein injection, and melatonin group which was intraperitoneally administrated with 2 successive doses of melatonin (50 mg/kg each) at a 2-hour interval. Pancreatic tissue and blood samples were taken from animals of all groups. IL-1β, TNF-α, and IL-10 levels were determined in blood samples. Apoptosis was determined by the TUNEL assay and the NF-κB was detected immunohistochemically in acinar cells of the exocrine pancreatic portion. IL-1β, TNF-α, and IL-10 levels in the acute pancreatitis group were significantly increased when compared to the control negative group. IL-1β and TNF-α levels in the melatonin-treated pancreatitis group were significantly lower than those of the acute pancreatitis group. While number of apoptotic cells and percentage of NF-κB immunopositive cells in the acute pancreatitis group were significantly increased compared to other groups and it was observed that these parameters were significantly reduced in the melatonin-treated pancreatitis group compared to the acute pancreatitis group. These findings suggest that melatonin administration can significantly reduce the severity of acute pancreatitis in rats.