Current Medical Treatment for Alcohol-Associated Liver Disease.

Alcohol-associated liver disease is one of the main causes of chronic liver disease. It comprises a clinical-histologic spectrum of presentations, from steatosis, steatohepatitis, to different degrees of fibrosis, including cirrhosis and severe necroinflammatory disease, called alcohol-associated hepatitis. In this focused update, we aim to present specific therapeutic interventions and strategies for the management of alcohol-associated liver disease. Current evidence for management in all spectra of manifestations is derived from general chronic liver disease recommendations, but with a higher emphasis on abstinence and nutritional support. Abstinence should comprise the treatment of alcohol use disorder as well as withdrawal syndrome. Nutritional assessment should also consider the presence of sarcopenia and its clinical manifestation, frailty. The degree of compensation of the disease should be evaluated, and complications, actively sought. The most severe acute form of this disease is alcohol-associated hepatitis, which has high mortality and morbidity. Current treatment is based on corticosteroids that act by reducing immune activation and blocking cytotoxicity and inflammation pathways. Other aspects of treatment include preventing and treating hepatorenal syndrome as well as preventing infections although there is no clear evidence as to the benefit of probiotics and antibiotics in prophylaxis. Novel therapies for alcohol-associated hepatitis include metadoxine, interleukin-22 analogs, and interleukin-1-beta antagonists. Finally, granulocyte colony-stimulating factor, microbiota transplantation, and gut-liver axis modulation have shown promising results. We also discuss palliative care in advanced alcohol-associated liver disease.

Transcription Factor AhR, Cytokines IL-6 and IL-22 in Subjects with and without Peri-Implantitis: A Case Control-Study.

Peri-implantitis is a plaque-associated condition characterized by mucosal inflammation and subsequent progressive loss of supporting bone; it is caused by bacterial biofilm, but the host response triggered by bacterial stimulation promotes the release of cells and mediators that culminate in tissue destruction. The Aryl-hydrocarbon Receptor (AhR) is associated with IL-22 production by Th22 and Th17 CD4+ Th cells. The presence of IL-6 may promote the Th22 phenotype. The present case-control study evaluated the gene expression of AhR, IL-22, and IL-6 in the peri-implant tissues of healthy and peri-implantitis patients. Tissue biopsies were collected from thirty-five volunteers (15 healthy and 20 with peri-implantitis). A real-time PCR reaction was utilized to assess the AhR, IL-22, and IL-6 gene expression levels relative to the reference gene (GAPDH). The results were analyzed using the Mann-Whitney test with a significance level of 5%. Higher levels of gene expression of AhR and IL-6 were detected in peri-implantitis tissues. The IL-22 gene expression levels did not differ between groups. In conclusion, higher gene expression levels for AhR and IL-6 were detected in the soft tissues of peri-implantitis patients. IL-22 did not vary between conditions, which may indicate the loss of the immunomodulatory role of IL-22 in periimplantitis.

Liver expression of IL-22, IL-22R1 and IL-22BP in patients with chronic hepatitis C with different fibrosis stages.

AIMS: Liver fibrosis is the result of an exacerbated wound-healing response associated with chronic liver injury. Interleukin-22 (IL-22) plays a key role in liver disease, through either a protective or an adverse role, depending on the context. The relationship between IL-22 and its receptors IL-22R1 and IL-22BP (soluble inhibitor) in liver fibrosis is unknown. In this study, we assessed the presence and quantity of IL-22, IL-22R1, and IL-22BP-producing cells in liver tissues of patients with chronic hepatitis C. METHODS AND RESULTS: The number of IL-22-producing cells was significantly higher in stages F1, F2, and F3 when compared to F0 or F4 (p < 0.05). The immunostaining of IL-22R1 decreased as liver fibrosis increased from F1 to F4. On the other hand, the concentration of IL-22BP-producing cells was higher in patients with cirrhosis (F4). Furthermore, the IL-22BP:IL-22 ratio was highest in patients with cirrhosis. CONCLUSIONS: Our results suggest that IL-22, IL-22R1 and IL-22BP may be involved in the mechanisms of liver fibrosis in patients with chronic hepatitis C.

From intestinal dysbiosis to alcohol-associated liver disease.

Alcohol-associated intestinal dysbiosis and bacterial overgrowth can lead to a dysregulation of tryptophan metabolism and lower production of indoles. Several of these indole derivatives are aryl hydrocarbon receptor ligands that, in turn, are involved in antimicrobial defense via induction of interleukin-22 (IL-22). IL-22 increases the expression of intestinal regenerating islet-derived 3 (Reg3) lectins, which maintain low bacterial colonization of the inner mucus layer and reduce bacterial translocation to the liver. Chronic alcohol consumption is associated with reduced intestinal expression of Reg3ß and Reg3γ, increased numbers of mucosa-associated bacteria and bacterial translocation. Translocated microbial products and viable bacteria reach the liver and activate the innate immune system. Release of inflammatory molecules promotes inflammation, contributes to hepatocyte death and results in a fibrotic response. This review summarizes the mechanisms by which chronic alcohol intake changes the gut microbiota and contributes to alcohol-associated liver disease by changing microbial-derived metabolites.

Los niveles séricos de Interleucina 22 e Interleucina 6 disminuyen luego del tratamiento en pacientes con artritis reumatoidea / Interleukin 22 and Interleukin 6 Serum Levels Decrease After Treatment in Rheumatoid Arthritis Patients

Introducción: La artritis reumatoidea se caracteriza por inflamación de la membrana sinovial debido al infiltrado de células inmunitarias que secretan citocinas relacionadas a perfil Th17 como IL-22 e IL-6. La dinámica de estas citocinas durante el tratamiento permanece incomprendida. El objetivo fue evaluar los niveles séricos y en líquido sinovial (LS) de IL-22 e IL-6, correlacionarlos con diferentes parámetros bioquímicos y clínicos y medir sus cambios post-tratamiento. Material y métodos: Se estudiaron 77 pacientes con AR y 30 controles. A 30 pacientes se los evaluó nuevamente luego de 3 meses de tratamiento y a 12 se les extrajo LS. Se midió VSG, PCR, FR, anti-CCPhs, IL-22 e IL-6. Se evaluó la actividad con DAS28 y respuesta al tratamiento con criterios EULAR. Resultados: IL-22 e IL-6 fueron similares entre pacientes y controles. Sus niveles disminuyeron luego del tratamiento, principalmente en pacientes respondedores. IL-22 fue menor e IL-6 mayor en LS que en sangre. IL-6 correlacionó positivamente con PCR y anti-CCPhs. Los niveles de VSG, PCR y DAS28 fueron mayores en pacientes con valores dosables de IL-6 que en no dosables. Conclusión: En pacientes con valores basales dosables de IL-22 e IL-6, los niveles de estas citocinas podrían utilizarse como marcador adicional de respuesta al tratamiento.

Introduction: Rheumatoid arthritis is characterized by synovium inflammation due to the infiltration of immune cells that secrete Th17 cytokines like IL-22 and IL-6. The dynamics of these cytokines during the treatment remain unknown. The aim of this study was to evaluate the levels of IL-22 and IL-6 serum and synovial fluid (SF) in correlation with different biochemical and clinical parameters and treatment-associated changes. Material and methods: Seventy-seven RA patients and 30 controls were recruited. Thirty patients were evaluated after 3 months of treatment and SF was collected of 12 patients. ESR, CRP, RF, anti-CCP hs, IL-22 e IL-6 were measured. DAS28 was used to assess disease activity and response to treatment followed EULAR criteria. Results: There were not differences in serum IL-22 and IL-6 levels between patients and controls. Cytokine levels decreased after treatment, mainly in responder patients. IL-22 was decreased and IL-6 was increased in SF compared to serum. IL-6 correlated positively with CRP and anti-CCPhs. ESR, CRP and DAS28 were increased in patients with detectable IL-6 compared to those with undetectable IL-6. Conclusion: In patients with detectable serum IL-22 and IL-6 levels before treatment initiation, follow-up of cytokine levels could be an useful additional tool to evaluate treatment response.

IL-22-expressing CD4+ AhR+ T lymphocytes are associated with RANKL-mediated alveolar bone resorption during experimental periodontitis.

BACKGROUND AND OBJECTIVE: Over the past few years, the importance of interleukin-22 (IL-22) and T-helper (Th)22 lymphocytes in the pathogenesis of periodontitis has become apparent; however, there are still aspects that are not addressed yet. Cells expressing IL-22 and aryl hydrocarbon receptor (AhR), transcription factor master switch gene implicated in the differentiation and function of Th22 lymphocytes, have been detected in periodontal tissues of periodontitis-affected patients. In addition, IL-22 has been associated with osteoclast differentiation and their bone resorptive activity in vitro. However, the destructive potential of IL-22-expressing AhR+ Th22 lymphocytes over periodontal tissues during periodontitis has not been demonstrated in vivo yet. Therefore, this study aimed to analyze whether IL-22-expressing CD4+ AhR+ T lymphocytes detected in periodontal lesions are associated with alveolar bone resorption during experimental periodontitis. MATERIAL AND METHODS: Using a murine model of periodontitis, the expression levels of IL-22 and AhR, as well as the Th1-, Th2-, Th17- and T regulatory-associated cytokines, were analyzed in periodontal lesions using qPCR. The detection of CD4+ IL-22+ AhR+ T lymphocytes was analyzed in periodontal lesions and cervical lymph nodes that drain these periodontal lesions using flow cytometry. In addition, the expression of the osteoclastogenic mediator called receptor activator of nuclear factor-κB ligand (RANKL) was analyzed by qPCR, western blot, and immunohistochemistry. Finally, alveolar bone resorption was analyzed using micro-computed tomography and scanning electron microscopy, and the bone resorption levels were correlated with IL-22 and RANKL expression. RESULTS: Higher levels of IL-22, AhR, and RANKL, as well as IL-1ß, IL-6, IL-12, IL-17, IL-23, and TNF-α, were expressed in periodontal lesions of infected mice compared with periodontal tissues of sham-infected and non-infected controls. Similarly, high RANKL immunoreaction was observed in periodontal tissues of infected mice; however, few or absent RANKL immunoreaction was observed in controls. This association between RANKL and periodontal infection was ratified by western blot. Furthermore, a higher detection of CD4+ IL-22+ AhR+ T lymphocytes was found in periodontal lesions and cervical lymph nodes that drain these periodontal lesions in infected mice compared with non-infected controls. Finally, the increased IL-22 and RANKL expression showed positive correlation between them and with the augmented alveolar bone resorption observed in experimental periodontal lesions. CONCLUSION: This study demonstrates the increase of IL-22-expressing CD4+ AhR+ T lymphocytes in periodontitis-affected tissues and shows a positive correlation between IL-22, RANKL expression, and alveolar bone resorption.

Carbohydrate and lipid disorders and adipokines levels in relation to body mass index in hypertensive patients / Trastorno del metabolismo de carbohidratos y lípidos y los niveles de adipoquinas en relación con el índice de masa corporal en pacientes con hipertensión

Abstract: Obesity is considered as a valid risk factor for cardiovascular disease, due to the fact that the risk of morbidity and mortality from various causes in obese people is significantly higher. Exact mechanisms of metabolic disorders in hypertension with obesity is still discussible. The aim of the study - to determine the peculiarities of carbohydrate, lipid metabolism changes and activity of adipokines and interleukin-22, in patients with hypertension according to nutritional status. Methods: 80 patients (37 males and 43 females) with essential hypertension (EH) of average age 60.17 years were examined. Carbohydrate, lipid profiles, apolipoprotein B (apo B), tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), adiponectin, interleukin-22 (IL-22) were estimated. Results: In patients with EH and obesity was found carbohydrates metabolism abnormalities, that was manifested as hyperinsulinemia, glucose and HbA1c levels elevation and insulin resistance (according to HOMA index). Lipid metabolism disorders were observed as valid increasing of triglycerides and apo B. Body mass index elevation was associated with progressive increasing of TNF-α and PAI-1 concentration with reducing of adiponectin level in the patients with EH. Positive relationships between TNF- and HbA1c, apo B; PAI-1 with glucose levels: negative correlation adiponectin with body mass and waist to hip ratio were detected in the patients with obesity associated (BMI ≥ 30 kg/m2) EH. Positive significant correlations between apo B and insulin levels, HOMA index, and TNF-α concentration were defined. IL-22 in overweigh and obese patients was significantly higher, correlates negatively with HDL-C. Conclusion: In patients with EH and obesity the adipokine dysfunction was revealed, that correlates with carbohydrate and lipid parameters that indicate increased proinflammatory and prothrombogenic processes.(AU)

Resumen: La obesidad se considera un factor de riesgo válido para las enfermedades cardiovasculares, debido a que el riesgo de morbilidad y mortalidad por diversas causas en personas obesas es significativamente mayor. Los mecanismos exactos de los trastornos metabólicos en la hipertensión con obesidad todavía son discutibles. El objetivo del estudio - determinar las peculiaridades de los carbohidratos, los cambios en el metabolismo de los lípidos y la actividad de las adipoquinas y la interleucina 22, en pacientes con hipertensión según el estado nutricional. Métodos: Se examinaron 80 pacientes (37 hombres y 43 mujeres) con hipertensión esencial (HE) de edad promedio de 60.17 años. Se estimaron los perfiles de carbohidratos, lípidos, apolipoproteína B (apo B), factor de necrosis tumoral-α (TNF-α), inhibidor activador del plasminógeno-1 (PAI-1), adiponectina, interleucina-22 (IL-22). Resultados: En pacientes con HE y obesidad se encontraron anomalías en el metabolismo de los carbohidratos, que se manifestaron como hiperinsulinemia, elevación de los niveles de glucosa y HbA1c y resistencia a la insulina (según el índice HOMA). Se observaron trastornos del metabolismo de los lípidos como aumento válido de triglicéridos y apo B. La elevación del índice de masa corporal se asoció con el aumento progresivo de la concentración de TNF-α y PAI-1 con la reducción del nivel de adiponectina en los pacientes con HE. Relaciones positivas entre TNF- y HbA1c, apo B; PAI-1 con niveles de glucosa: se detectaron correlaciones negativas de adiponectina con masa corporal y relación cintura-cadera en los pacientes con obesidad (IMC ≥ kg/m2) asociada con HE. Se definieron correlaciones positivas significativas entre los niveles de apo B e insulina, el índice HOMA y la concentración de TNF-α. La IL-22 en pacientes con sobrepeso y obesos fue significativamente mayor, se correlaciona negativamente con HDL-C. Conclusión: En pacientes con HE y obesidad se reveló la disfunción de la adipoquina, que se correlaciona con parámetros de carbohidratos y lípidos que indican un aumento de los procesos proinflamatorios y protrombogénicos.(AU)

Th1/Th17/Th22 immune response and their association with joint pain, imagenological bone loss, RANKL expression and osteoclast activity in temporomandibular joint osteoarthritis: A preliminary report.

It is well accepted that the presence of cytokines belonging to the Th1/Th17/Th22 axis of immuno-inflammatory response in the joint environment, such as IL-1ß, IL-17 and IL-22, respectively, are associated with pathogenesis of several synovial joint degenerative disorders. During temporomandibular joint osteoarthritis (TMJ-OA), IL-1ß and IL-17 have been implicated in the inflammation and resorption of sub-chondral bone; however, the role of Th22 response in the TMJ-OA pathophysiology has not been established. This study aimed to compare the expression of Th1/Th17/Th22-type cytokines, chemokines and chemokine receptors in synovial fluid samples obtained from TMJ-OA or disk displacement with reduction (DDWR) patients. In addition, it aimed to associate these levels with joint pain, imagenological signs of bone degeneration, RANKL production, osteoclastogenesis and osteoclast-induced bone resorption. Higher levels of IL-1ß, IL-17 and IL-22 were expressed in TMJ-OA compared with DDWR subjects, and these increased levels significantly correlated with RANKL expression, joint pain and articular bone degeneration. Higher levels of CCR5, CCR6 and CCR7, as well as their respective ligands CCL5 and CCL20, responsible for recruitment of IL-1ß, IL-17 and IL-22-producing cells, were over-expressed in TMJ-OA compared with DDWR subjects. Osteoclastogenesis and osteoclast-induced bone resorption were significantly greater in presence of synovial fluid from TMJ-OA compared with DDWR subjects. These data demonstrate that cytokines, CCLs and CCRs associated with the Th1/Th17/Th22 axis of immuno-inflammatory response are involved in TMJ-OA pathogenesis. These findings suggest that IL-22 is involved in the RANKL expression in TMJ-OA, which in turn induces differentiation of osteoclasts and subsequent resorption of sub-chondral bone.

Increased levels of the T-helper 22-associated cytokine (interleukin-22) and transcription factor (aryl hydrocarbon receptor) in patients with periodontitis are associated with osteoclast resorptive activity and severity of the disease.

BACKGROUND AND OBJECTIVE: Two new T-helper (Th) phenotypes have been recently described and named Th9 and Th22 lymphocytes; however, their role in the pathogenesis of periodontitis remains unclear. This study was aimed to assess whether Th9 and Th22 lymphocytes, through interleukin (IL)-9 and IL-22 production, respectively, are associated with the severity of periodontitis and bone resorption. MATERIAL AND METHODS: Gingival crevicular fluid samples and biopsies were obtained from patients with moderate-to-advanced chronic periodontitis and gingivitis, and healthy controls. The levels for the Th9 and Th22-associated cytokines and master-switch transcription factors Spi-B and aryl hydrocarbon receptor (AhR) were quantified by enzyme-linked immunosorbent assay, real-time reverse-transcription quantitative polymerase chain reaction and flow cytometry. In addition, the osteoclast activity in response to tissue homogenates from periodontitis and healthy samples was analyzed quantifying the number of TRAP-positive cells and areas of bone resorption pits produced, in the presence or absence of recombinant human IL-22 and anti-IL-22 neutralization antibody. RESULTS: Higher levels of IL-22 and AhR were detected in patients with periodontitis compared with gingivitis and healthy individuals. In addition, higher levels of IL-9 and Spi-B were detected in gingivitis patients compared with periodontitis and healthy individuals. In patients with periodontitis, a significant positive correlation was detected between secreted levels of IL-22 and clinical attachment level of the sampled periodontal pockets. When osteoclasts were exposed to tissue homogenates obtained from patients with periodontitis, higher levels of resorptive activity were observed as compared with the same cells exposed to tissue homogenates obtained from healthy individuals, and this increment was dependent on the presence and neutralization of IL-22. CONCLUSION: Increased levels of IL-22 produced by Th22 lymphocytes are associated with the pathogenesis of periodontitis, in particular, with osteoclast resorptive activity and severity of disease.

What goes around comes around: novel pharmacological targets in the gut-brain axis.

The gut and the brain communicate bidirectionally through anatomic and humoral pathways, establishing what is known as the gut-brain axis. Therefore, interventions affecting one system will impact on the other, giving the opportunity to investigate and develop future therapeutic strategies that target both systems. Alterations in the gut-brain axis may arise as a consequence of changes in microbiota composition (dysbiosis), modifications in intestinal barrier function, impairment of enteric nervous system, unbalanced local immune response and exaggerated responses to stress, to mention a few. In this review we analyze and discuss several novel pharmacological targets within the gut-brain axis, with potential applications to improve intestinal and mental health.

Interleukin-17- and interleukin-22-secreting myelin-specific CD4(+) T cells resistant to corticoids are related with active brain lesions in multiple sclerosis patients.

Multiple sclerosis (MS) is thought to be an autoimmune disorder. It is believed that immunological events in the early stages have great impact on the disease course. Therefore, we aimed to evaluate the cytokine profile of myelin basic protein (MBP)-specific T cells from MS patients in the early phase of the disease and correlate it to clinical parameters, as well as to the effect of in vitro corticoid treatment. Peripheral T cells from MS patients were stimulated with MBP with our without hydrocortisone for 5 days. The cytokines level were determined by ELISA. The number of active brain lesions was determined by MRI scans, and the neurological disabilities were assessed by Expanded Disability Status Scale scores. Our results demonstrated that MS-derived T cells responded to MBP by producing high levels of T helper type 1 (Th1) and Th17 cytokines. Although the production of interleukin-6 (IL-6), granulocyte-macrophage colony-stimulating factor, IL-17 and IL-22 was less sensitive to hydrocortisone inhibition, only IL-17 and IL-22 levels correlated with active brain lesions. The ability of hydrocortisone to inhibit IL-17 and IL-22 production by MBP-specific CD4(+) T cells was inversely related to the number of active brain lesions. Finally, the production of both cytokines was significantly higher in cell cultures from Afrodescendant patients and it was less sensitive to hydrocortisone inhibition. In summary, our data suggest that IL-17- and IL-22-secreting CD4(+) T cells resistant to corticoids are associated with radiological activity of the MS in early stages of the disease, mainly among Afrodescendant patients who, normally, have worse prognosis.

Association between interleukin-22 genetic polymorphisms and bladder cancer risk

OBJECTIVE:The cytokine interleukin-22 (IL-22), which is produced by T cells and natural killer cells, is associated with tumorigenesis and tumor progression in cancers. However, the role of IL-22 in bladder cancer has not been investigated.MATERIALS AND METHODS:A prospective hospital-based case-control study comprising 210 patients with pathologically proven bladder cancer and 210 age- and gender-matched healthy controls was conducted. The genotypes of 3 common polymorphisms (-429 C/T, +1046 T/A and +1995 A/C) of the IL-22 gene were determined with fluorogenic 5' exonuclease assays.RESULTS:Patients with bladder cancer had a significantly higher frequency of the IL-22 -429 TT genotype [odds ratio (OR)=2.04, 95% confidence interval (CI)=1.19, 3.49; p=0.009] and -429 T allele (OR=1.42, 95% CI=1.08, 1.87; p=0.01) than the healthy controls. These findings were still significant after a Bonferroni correction. When stratifying according to the stage of bladder cancer, we found that patients with superficial bladder cancer had a significantly lower frequency of the IL-22 -429 TT genotype (OR=0.48, 95% CI=0.23, 0.98; p=0.04). When stratifying according to the grade and histological type of bladder cancer, we found no statistical association. The IL-22 +1046 T/A and IL-22 +1995 A/C gene polymorphisms were not associated with the risk of bladder cancer.CONCLUSION:To the authors' knowledge, this is the first report documenting that the IL-22 -429 C/T gene polymorphism is associated with bladder cancer risk. Additional studies are required to confirm this finding.

Absence of interleukin 22 affects the oral microbiota and the progression of induced periapical lesions in murine teeth.

AIM: To evaluate the absence of IL-22 on the progression of periapical lesions in wild-type (WT) and IL-22 knockout (IL-22 KO) mice. METHODOLOGY: The evaluation of the oral microbial profile of mice was performed by Checkerboard DNA-DNA hybridization from saliva samples. Periapical lesions were induced in manbibular first molars by pulpal exposure and evaluated after 7, 21 and 42 days (n = 15). Haematoxylin-eosin-stained sections were analysed under conventional and fluorescence microscopy to evaluate the tissue features and size of periapical lesions and tartrate-resistant acid phosphatase histoenzymology (TRAP), Brown & Brenn staining and immunohistochemistry. The scores of the number of bacterial cells present in the oral cavity were analysed by the Mann-Whitney test, and the results and comparisons for periapical lesion size and number of osteoclasts were subjected to one-way anova and Bonferroni's post-test (α = 0.05). RESULTS: Significant differences were observed for bacterial load between the groups of animals for 6 bacterial species (P < 0.05), with five species found in higher levels in the WT group, and one in the IL-22 KO group. WT mice had significantly larger periapical lesions (P < 0.05) between 7 and 42 days and between 21 and 42 days, with an increase in the mean size and number of osteoclasts. IL-22 KO mice had an increase in periapical lesion size and number of osteoclasts between 7 and 21 days (P < 0.05). No differences were found between bacteria localization in the root canal system between the experimental groups. Small variations related to the location of immunostaining were found between the groups. CONCLUSION: This study revealed differences in the composition of oral microbiota between mice that may be taken into account in the susceptibility to infections and development of periapical lesions. The absence of IL-22 in mice resulted in smaller periapical lesions with fewer osteoclasts at the final experimental period, suggesting the participation of IL-22 in the host immune and inflammatory response to a periradicular infection.

3-D modeling and molecular dynamics simulation of interleukin-22 from the So-iny mullet, Liza haematocheila

Background: Interleukin-22 (IL-22) plays an important role in the regulation of immune responses. However, little is known about its function or structure in fish. Results: The IL-22 gene was first cloned from So-iny mullet (Liza haematocheila), one of commercially important fish species in China. Then, 3-D structure model of the mullet IL-22 was constructed by comparative modeling method using human IL-22 (1M4R) as template, and a 5 ns molecular dynamics (MD) was studied. The open reading frame (ORF) of mullet IL-22 cDNA was 555 bp, encoding 184 amino acids. The mullet IL-22 shared higher identities with the other fish IL-22 homologs and possessed a conserved IL-10 signature motif at its C-terminal. The mullet IL-22 model possessed six conserved helix structure. PROCHECK, SAVES and Molprobity server analysis confirmed that this model threaded well with human IL-22. Strikingly, analysis with CastP, cons-PPISP server suggested that the cysteines in mullet IL-22 might not be involved in the forming of disulfide bond for structural stabilization, but related to protein-protein interactions. Conclusions: The structure of IL-22 in So-iny mullet (Liza haematocheila) was constructed using comparative modeling method which provide more information for studying the function of fish IL-22.