Neutralization of TGF-β in combination with IL-6 ameliorates septic arthritis by altering RANKL/OPG interaction in murine lymphocytes

Abstract

Septic arthritis is an inflammatory joint disease caused by S. aureus. Hematogenous entry of the bacteria to the joint space secretes
pro-inflammatory cytokines TGF-β and IL-6, which alter the Th17/Treg switch. Inhibition of TGF-β and IL-6 to modulate Th17/Treg
homeostasis and RANKL/OPG interaction are not done so far in septic arthritis. Role of lymphocyte-derived TGF-β, IL-10, IL-21 along
with OPN, OPG, cellular H2O2, SOD and catalase activities, and the expressions of RANKL and MMP2 were studied in total lymphocytes
of blood, spleen and synovial tissues of Swiss albino mice treated with antibody against TGF-β along with IL-6 Ab after induction of
septic arthritis. Simultaneous neutralization of TGF-β along with IL-6 is effective in shifting the Th17 cell into Treg cell of the arthritic
mice and modulates RANKL and MMP2 expression that leads to the down-regulation of osteoclastic activity and reduces the production of OPN. Additionally, such treatment reduces oxidative stress via enhancing the activities SOD and catalase enzymes in lymphocytes. So, simultaneous neutralization of TGF-β and IL-6 reduces S. aureus infection-associated inflammatory joint damage by increasing Treg numbers and decreasing the number of pro-inflammatory Th17 cells.