Lack of cross tolerance between LPS and muramyl dipeptide in induction of circulating TNF-alpha and IL-6 in guinea pigs.
In guinea pigs, lipopolysaccharide (LPS) from gram-negative bacteria and muramyl dipeptide (MDP) from gram-positive bacteria are potent inducers of systemic production of proinflammatory cytokines and fever. However, there is a striking difference between these two bacterial pyrogens in so far as repeated administration of LPS, but not of MDP, in short-term intervals induces tolerance by a progressive downregulation of the systemic cytokine network. In the present study, we investigated MDP-induced fever and the systemic release of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) in LPS-tolerant guinea pigs in comparison with naive animals. Endotoxin tolerance was induced by repeated intramuscular injections of 20 microg/kg LPS at intervals of 3 days. In response to the last of five injections with LPS, systemic production of TNF-alpha and IL-6 as well as the development of a febrile response was abrogated almost completely. Those guinea pigs that had developed an LPS tolerance could, however, produce the same amounts of TNF-alpha and IL-6 as naive animals in response to a challenge with MDP. Also, MDP-induced fever was identical in LPS-tolerant and naive guinea pigs. These results provide evidence for a lack of cross tolerance between LPS and MDP in induction of circulating cytokines and fever in guinea pigs.
Roth
J
J
Physiologisches Institut, Klinikum der Justus-Liebig-Universität, Giessen, Germany.
Aslan
T
T
Störr
B
B
Zeisberger
E
E
D000119:Acetylmuramyl-Alanyl-Isoglutamine / Q000494:pharmacology*; D000818:Animals; D016207:Cytokines / Q000096:biosynthesis; D004361:Drug Tolerance; D005334:Fever / Q000139:chemically induced; D006168:Guinea Pigs; D015850:Interleukin-6 / Q000097:blood*; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D016207:Cytokines; D015850:Interleukin-6; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D000119:Acetylmuramyl-Alanyl-Isoglutamine