Immuno-Modulatory Effect and Therapeutic Potential of Brugia malayi Cystatin in Experimentally Induced Arthritis

Abstract

Helminths are known to modulate host's immune system and understanding this modulation can help in identification of novel therapeutic agents for autoimmune diseases. In this study, we have assessed the immune-modulatory activity and the therapeutic effect of Brugia malayi recombinant cystatin (rBmCys) in methylated BSA (mBSA) induced arthritis using rodent model. Administration of rBmCys has suppressed the severity of mBSA-arthritis in mastomys by reducing paw swelling and other clinical disease parameters as evident from significantly decreased arthritic index. The anti-arthritic effect of rBmCys was also confirmed by decreased histopathological score for synovitis, bone erosion and fibrosis in the tissue sections of paws. Further, this therapeutic effect of cystatin was found to be associated with significantly decreased production of IFN-c and TNF-a and increased release of IL-4 and IL-10 cytokines. These results implied that rBmCys treatment has alleviated mBSA-induced arthritis and thus can be a promising alternative agent for the treatment of arthritis.

Evaluating the preventive and curative effects of Toxocara canis larva in Freund's complete adjuvant‐induced arthritis

“…The study of TGF-β in T-cell responses has shown differential results as an inhibitor or promoter of the inflammatory response. 11 In a recent study of patients with Sjögren's Syndrome and rheumatoid arthritis and a control group, it was concluded that TGF-β levels significantly decreased in rheumatoid arthritis patients. Researchers have also shown that TGF-β plays a role in fibrosis, which is often associated with inflammatory disease.…”

“…8 Several studies on experimentally induced autoimmune disorders have shown that helminths or the products derived from them can alter the severity of allergy and autoimmune conditions via modulation of the host immune system, suppression of interferon gamma 10 Based on these studies, utilization of helminths or their products in the treatment of RA has been conceptualized. 11 The purpose of this study was to show that in rats experimentally infected with T canis significantly less joint inflammation was observed following intra-articular injection of Freund's complete adjuvant (FCA) in comparison with non-infected FCA-treated animals.…”

Parasite Cystatin: Immunomodulatory Molecule with Therapeutic Activity against Immune Mediated Disorders

“…This disease affects approximately 54.4 million (25%) people in the United States and is estimated to affect over 78 million by 2040 [ 109 ]. Several studies show that both preventive and therapeutic administration of B. malayi cystatin could suppress the severity of mBSA-induced arthritis [ 97 , 98 ]. Treated animals showed a reduction in paw swelling and a reduction in clinical disease parameters accompanied by a Th2 dominant immune response [ 97 , 98 ].…”

“…Several studies show that both preventive and therapeutic administration of B. malayi cystatin could suppress the severity of mBSA-induced arthritis [ 97 , 98 ]. Treated animals showed a reduction in paw swelling and a reduction in clinical disease parameters accompanied by a Th2 dominant immune response [ 97 , 98 ]. Collagen-induced arthritis in DBA/1 mice was significantly attenuated following rSjCystatin treatment.…”

“…These treated mice had upregulation of Treg cells and a skewed Th2 dominant immune response in the periphery with inhibition of Th1 and Th17 immune responses [ 101 ]. The mechanism of cystatin-induced suppression of arthritis appears to be a general suppression of RANKL (receptor activator of nuclear factor kappa-B ligand) expression in osteoclasts [ 97 ]. RANKL is essential for differentiation and activation of osteoclasts and synoviocytes [ 110 ].…”