Thymulin reverses inflammatory hyperalgesia and modulates the increased concentration of proinflammatory cytokines induced by i.c.v. endotoxin injection.
The immunomodulatory thymic hormone thymulin has been shown previously to possess anti-inflammatory actions in the periphery. In this study, we have examined the effect of i.c.v. injections of either endotoxin (ET) or thymulin, in separate groups of conscious rats, on pain-related behavior and cytokine levels in different areas of the brain. Furthermore, we investigated the effect of pretreatment with either i.c.v. or i.p. injections of thymulin on endotoxin-induced hyperalgesia and the effect of pretreatment with i.c.v. thymulin on endotoxin-induced up-regulation of cytokine levels. Our results demonstrate that i.c.v. injection of endotoxin (1 microg in 5 microl saline) resulted in a significant decrease in the nociceptive thresholds as assessed by different pain tests, with peak hyperalgesia at 3 h. However, thymulin at different doses, when injected (i.c.v.), had no significant effect on pain related behavior. Pretreatment (i.c.v.) with thymulin (0.1, 0.5 and 1 microg in 5 microl saline) 20 min before endotoxin (i.c.v.) injection (1 microg in 5 microl saline) reduced, in a dose dependent manner, the endotoxin-induced hyperalgesia and exerted differential effects on the up-regulated levels of cytokines in different areas of the brain. The results provide behavioral and immunochemical characterization of a rat model for intracerebral inflammation and indicates a neuroprotective role for thymulin in the CNS.
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, Riad El Solh, Beirut 1107-2020, Lebanon. bared@aub.edu.lb
B
B
Safieh-Garabedian
C I
CI
Ochoa-Chaar
S
S
Poole
C A
CA
Massaad
S F
SF
Atweh
S J
SJ
Jabbur
N E
NE
Saadé
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors* / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions / Q000502:physiology; D004660:Encephalitis / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D004731:Endotoxins / Q000494:pharmacology*; D006930:Hyperalgesia / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D007276:Injections, Intraventricular; D008297:Male; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013935:Thymic Factor, Circulating / Q000276:immunology / Q000494:pharmacology*
D016207:Cytokines; D004731:Endotoxins; D013935:Thymic Factor, Circulating