Neutrophil Is Involved In The Progress Of Rheumatoid Arthritis Via Maturation Of IL-33

Objectives:Neutrophil and interleukin-33(IL-33) were involved in the development of rheumatoid arthritis(RA), but the mechanism of RA is still no understood. Elastase from neutrophil cut full-length IL-33into the mature IL-33form, and the mature IL-33have a higher biological activity than full IL-33. There was no reports about mature IL-33is participated in the progress of disease related IL-33. The author presume neutrophil exacerbate inflammation of rheumatoid arthritis via maturation of EL-33.Methods:IL-33in serum of RA and healthy volunteers and in synovial fluid of RA and OA were detected by ELISA, neutrophil in synovial fluid of RA and OA were checked by Wright-Giemsa staining. To set up CIA animal model, prepare the emulsion with collagen and inject subcutaneously in the tail of DBA/1mice on day0and21. The initial injection using CFA containing1mg/ml of Mtuberculosis, a booster injection using IFA. Mice were sacrificed at clinic score4of signal affected limb. The level of IL-33and elastase in joints homogenate were measured by ELISA, elastase activity was tested by light absorption spectrometry. Full IL-33and mature IL-33were inspected by Western blot assay, HE stain for detection of affected limbs and neutrophil infiltrated. Neutrophil were depleted with anti-Grl in CIA mice,and detected above index on day42.Results:The level of IL-33in serum of RA are higher than healthy volunteers (p<0.01), there is no significance in synovial fluid between RA and OA(p>0.05). The percent of neutrophil in synovial fluid of RA are higher than OA(p<0.01). The level of IL-33> elastase and elastase activity in joints homogenate of CIA group are higher than control groups (p<0.05), and mature IL-33is found in peak status, Inflamed limbs are infiltrated with neutrophil. Neutrophil depleted with anti-Grl could delay the emergence of arthritis, the red and swelling joints is found on day27, inflammation is more serious with times gone, and weigh lost, there is high level of IL-33in joints homogenate, but no mature IL-33on day42.Conclusion:1.The level of IL-33in serum of RA is related with disease.2.Mature IL-33is involved in the progress of CIA, and is associated with the degree of inflammation in CIA joint.3.Neutrophil cut full IL-33into mature IL-33via elastase,which is involved in inflammation related CIA.