title: Immunomodulatory Effect of Chymotrypsin in CNS Is Sex-independent: Evidence of Anti-inflammatory Role for IL-17 in EAE.
abstract: Multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE), are inflammatory autoimmune diseases of the central nervous system. Chymotrypsin is a serine protease with immunomodulatory effect in the peripheral organs. We previously demonstrated the immunomodulatory effect of chymotrypsin in ameliorating the EAE in female Lewis rats. However, there are sex-based differences in the immune system, drug activity, and CNS structure and composition. In addition, female gender is a better prognostic indicator of MS and males are more severely affected by EAE than females. Consequently, gender may have an important impact on therapeutic effect. Therefore, in this study we investigated the anti-inflammatory effect of chymotrypsin in male Lewis rat model of EAE. The disease was induced in male Lewis rats and the animals were evaluated for weight loss and clinical signs for 14 days. Intra-CSF injection of chymotrypsin was done on day 7 and expression of mRNA for IFN-γ, IL-4, IL-17, and FoxP3 in brain, spinal cord and deep cervical lymph node were determined using a two-step real-time PCR. Administration of 0.2mg/ml chymotrypsin ameliorated the disease by decreasing IFN-γ and increasing expression of IL-4 and IL-17 at the inflammatory foci. This is consistent with anti-inflammatory effect of IL-4 and IL-17 at high concentrations. We conclude that Immunomodulatory affect of chymotrypsin in CNS is sex-independent. Our result also provides more evidence on the anti-inflammatory role of IL-17. However more research is needed to elucidate the underlying immunomodulatory role of chymotrypsin and how to increase its beneficial effect by modification of dosage and/or regimen of administration.
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Ameneh
authors.initials: A
authors.lastname: Ghaffarinia
authors.affiliation: Medical Biology Research Center, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Shahram
authors.initials: S
authors.lastname: Parvaneh
authors.affiliation: Department of Anatomy, Medical School, Kermanshah University of Medical Sciences, Kermanshah, Iran.
authors.forename: Cyrus
authors.initials: C
authors.lastname: Jalili
authors.affiliation: Department of Immunology, Pasture Institute of Iran, Tehran, Iran.
authors.forename: Farhad
authors.initials: F
authors.lastname: Riazi-Rad
authors.affiliation: Department of Microbiology and Immunology, Medical School, Alborz University of Medical Sciences, Karaj, Iran.
authors.forename: Somayeh
authors.initials: S
authors.lastname: Yaslianifard
authors.affiliation: Department of Microbiology and Immunology, Medical School, Alborz University of Medical Sciences, Karaj Iran.
authors.forename: Nafiseh
authors.initials: N
authors.lastname: Pakravan
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology; D002918:Chymotrypsin / Q000633:toxicity*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D005260:Female; D007371:Interferon-gamma / Q000276:immunology; D020381:Interleukin-17 / Q000276:immunology*; D015847:Interleukin-4 / Q000276:immunology; D008297:Male; D009103:Multiple Sclerosis / Q000139:chemically induced / Q000276:immunology / Q000473:pathology; D051381:Rats; D011917:Rats, Inbred Lew; D012727:Sex Characteristics
chemical_list: C515934:Il17a protein, rat; D020381:Interleukin-17; D015847:Interleukin-4; D007371:Interferon-gamma; D002918:Chymotrypsin
keywords: Anti-inflammatory; CNS; Chymotrypsin; Experimental autoimmune encephalomyelitis; Immunomodulation; Interleukin-17; Male