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INFLAMMATION AND CYTOKINES
1Institute of Animal Sciences, Swiss Federal Institute of Technology, 8603 Schwerzenbach; 3Department of Research, University Hospital, 4031 Basel, Switzerland; and 2Bourne Laboratory, New York Presbyterian Hospital-Weill Cornell Medical College, White Plains, New York 10605
Submitted 14 November 2003 ; accepted in final form 25 March 2004
The cell surface component CD14 and the toll-like receptors 2 and 4 (TLR2 and TLR4) are important in mediating the immune responses to bacterial products in mammals. Using mice genetically deficient in CD14, TLR2, or TLR4, we studied the role of these molecules in the anorectic effects of LPS and muramyl dipeptide (MDP). CD14 or TLR2 knockout (KO) and TLR4-deficient (TLR4-DEF) mice as well as corresponding wild-type (WT) colittermates were injected intraperitoneally at dark onset with LPS (2 µg/mouse), MDP (10 mg/kg), interleukin-1
(IL-1
, 150 ng/mouse), or vehicle, and food intake was recorded. LPS and MDP reduced food intake in WT mice of all genotypes tested. The anorectic effect of LPS was attenuated (P < 0.04) in CD14-KO and TLR4-DEF mice but not in TLR2-KO (P > 0.05). The anorectic effect of MDP was blunted in CD14-KO and TLR2-KO (P < 0.02) mice but not in TLR4-DEF mice. IL-1
reduced food intake similarly in all genotypes tested. These results indicate that CD14 is involved in mediating the anorectic effects of both LPS and MDP. Furthermore, TLR4 and TLR2 are specifically involved in mediating the anorectic effects of LPS and MDP, respectively. The results are consistent with the hypothesis that TLR4 functions as the true LPS receptor and that TLR2 is involved in recognition of gram-positive bacterial products.
toll-like receptor 2 and 4; food intake; lipopolysaccharide; muramyl dipeptide; cytokines; interleukin-1
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