Suppression Of Inflammation And Modμlation Of Immune Activity By Cardiotoxin

Objective: To investigate analgesic and anti-inflammatory effects bof oraladministered cardiotoxin (CTX) in animal models of inflammation and to arthritis.Methods: To investigate the analgesic effects of CTX, hot plate test, acetic acidwrithing assay and formalin test were used. Egg white induced rat inflammation test,filter paper induced rat granμloma formation test, mouse abdominal capillarypermeability test and CFA induced primary inflammatory reaction were used toinvestigate the anti-inflammatory of CTX. Adjuvant arthritis (AA) was induced byintradermal injection of0.1ml CFA which contains10mg/ml Heat-killedMycobacterium tubercμlosis H37Ra (Mtb) into right paw or at the base of tail. Forevaluation of AA, we measured the swelling of paws and arthritic score. Meanwhile, theright ankle joints of rats were examined with histological assessment. The percentagesof CD4T cells from peripheral blood were determined with flow cytometric analysisand the levels of IL-6, IL-10and IL-17were determined with ELASA. In addition, weinvestigated the effects of CTX in fibroblast-like synoviocytes (FLS) from AArats.Resμlts: Our studies showed that orally administered CTX exerted analgesiceffects on animal models of inflammation. Orally administered CTX showedanti-inflammatory effects in egg white induced rat inflammation test, filter paperinduced rat granμloma formation test and mouse abdominal capillary permeability test.Meanwhile, orally pretreated with CTX suppresses CFA induced primary inflammatoryreaction. The present study also showed that oral administered CTX displayedanti-arthritic effects in AA model. Interestingly, orally administered CTX affectedcellμlar immune system, significantly decline CD4+T cells in AA rats. From our study,orally treated with CTX significantly inhibited the expression of IL-17and IL-6, buthad no effect on the anti-inflammatory cytokine IL-10. In vivo, CTX inhibitedexpression of IL-6in FLS and inhibited the expression of p-STAT3. Conclusions: Oral administration of CTX exerts analgesic, anti-inflammatory andanti-arthritic pharmacological effects. Meanwhile, orally administered CTX attenuatedthe severity of AA and reduced the CD4T cells in RA. In addition, CTX significantlyinhibited the expression of pro-inflammatory cytokines, including IL-17and IL-6. Thisstudy will provide new ideas for therapeutic strategies of arthritis.