title: Anti-Toll-like receptor 2 and 4 antibodies suppress inflammatory response in mice.
abstract: Toll-like receptors (TLRs) 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 TLR2 and TLR4 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-TLR2 and 4 antibodies may have a synergistic therapeutic effect on inflammatory disease in vivo.
authors.affiliation: Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow, UK.
authors.forename: Mousa
authors.initials: M
authors.lastname: Komai-Koma
authors.forename: Dong
authors.initials: D
authors.lastname: Li
authors.forename: Eryi
authors.initials: E
authors.lastname: Wang
authors.forename: Diane
authors.initials: D
authors.lastname: Vaughan
authors.forename: Damo
authors.initials: D
authors.lastname: Xu
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D001169:Arthritis, Experimental / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D005260:Female; D007111:Immunity, Cellular; D016130:Immunophenotyping; D007249:Inflammation / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000469:parasitology; D018320:Leishmania major / Q000276:immunology; D016773:Leishmaniasis, Cutaneous / Q000276:immunology / Q000378:metabolism; D051379:Mice; D011948:Receptors, Antigen, T-Cell / Q000378:metabolism; D051195:Toll-Like Receptor 2 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D011948:Receptors, Antigen, T-Cell; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4
keywords: anti-Toll-like receptor; inflammation; leishmaniasis; rheumatoid arthritis