Effect of thalidomide on the inflammatory response in cerebrospinal fluid in experimental bacterial meningitis.
In experimental bacterial meningitis in rabbits, the inflammatory process is largely mediated by cytokines such as IL-1 and TNF-alpha. Since thalidomide has been shown to inhibit TNF-alpha production, experiments were carried out to determine whether the drug can modulate the inflammatory response to either lysates of H. influenzae (gram negative) or heat killed S. pneumoniae (gram positive) in rabbits. The introduction of a lysate of H. influenzae into the CSF of rabbits causes a very acute inflammatory response, as indicated by a rapid increase in TNF-alpha levels in the CSF and a concomitantly rapid leukocytosis. In contrast, the introduction of heat killed S. pneumoniae, induces a more indolent inflammatory response which also wanes more slowly. Thalidomide treatment reduces TNF-alpha production in both experimental systems, but has a greater effect on the more indolent gram positive inflammatory response in which peak TNF-alpha levels in the CSF are reduced by > 50%. Also, a sustained inhibition of leukocytosis is observed in the inflammatory response to heat-killed gram positive bacteria. In meningeal inflammation induced by the Gram negative lysate, treatment with thalidomide results in only a 29% inhibition of TNF-alpha release into the CSF. In contrast to the drug effect on TNF-alpha, thalidomide treatment does not significantly affect IL-1 levels in these models of rabbit bacterial meningitis.
Burroughs
M H
MH
Laboratory of Cellular Physiology & Immunology, Rockefeller University, New York, N.Y. 10021, USA.
Tsenova-Berkova
L
L
Sokol
K
K
Ossig
J
J
Tuomanen
E
E
Kaplan
G
G
D000818:Animals; D002556:Cerebrospinal Fluid Proteins / Q000187:drug effects; D004195:Disease Models, Animal; D006801:Humans; D007249:Inflammation; D007375:Interleukin-1 / Q000134:cerebrospinal fluid*; D007962:Leukocytes; D008583:Meningitis, Haemophilus / Q000276:immunology*; D008586:Meningitis, Pneumococcal / Q000276:immunology*; D011817:Rabbits; D013792:Thalidomide / Q000493:pharmacokinetics / Q000494:pharmacology*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid*
D002556:Cerebrospinal Fluid Proteins; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; D013792:Thalidomide