Anti‐Toll‐like receptor 2 and 4 antibodies suppress inflammatory response in mice

Summary Toll‐like receptors ( TLR s) 2 and 4 recognize different endogenous and exogenous agonists and play a distinct role in infection and inflammation. However, their ultimate effect in a given infectious and inflammatory disease is less understood. We produced polyclonal anti‐murine TLR 2 and TLR 4 antibodies and investigated their effect on cutaneous leishmaniasis and inflammatory arthritis. Administration of these antibodies to susceptible BALB /c mice, infected in the footpad with Leishmania major , reduced footpad swelling but not the parasite load compared with mice treated with control IgG. The antibodies synergistically reduced leishmanial‐specific T‐cell proliferation, T helper type 1 and type 2 cytokine production, specific IgG1 and IgG2a antibody synthesis, and T ‐cell receptor and co‐stimulatory molecule expression on dendritic cells in infected mice. We then tested the effect of these antibodies on collagen‐induced arthritis ( CIA ) in DBA /1 mice, a classic model of chronic inflammation. Both antibodies markedly suppressed the development of clinical parameters with concomitant reduction of pro‐inflammatory cytokine production. These data therefore suggest that anti‐ TLR 2 and 4 antibodies may have a synergistic therapeutic effect on inflammatory disease in vivo .