The role of cytokines and prostaglandin-E(2) in thymulin induced hyperalgesia.
We have recently reported that intraperitoneal (i.p.) injection of thymulin at low doses (50 ng) resulted in thermal and mechanical hyperalgesia and upregulation of the level of interleukin-1beta in the liver. In this study, we demonstrate that such injections of thymulin result in a significant elevation in the levels of TNF-alpha (P<0.01), NGF (P<0.01) and PGE(2) (P<0.01) in the liver of the treated rats, in addition to the increase in the levels of IL-1beta. Pretreatment with specific antagonists to each of these factors (polyclonal anti-TNF-alpha, anti-NGF antiserum and IL-1 receptor antagonist) did not result in the abolition of the hyperalgesia as assessed by the paw pressure, hot plate, paw immersion and tail flick tests. However, pretreatment with a combination of the above antagonist and antisera almost completely prevented thymulin-induced hyperalgesia. The cyclooxygenase inhibitor, meloxicam, reversed in a dose dependent manner (0.2, 0.4 and 2 mg/kg) thymulin effects as assessed by the different pain tests. It also abolished the thymulin-induced increase in the level of cytokines and NGF in the liver. Our results indicate that PGE(2) could be the key mediator of the hyperalgesic action of thymulin and the observed upregulation of proinflammatory cytokines and NGF.
Safieh-Garabedian
B
B
Department of Biology, Faculty of Arts and Sciences, American University of Beirut, P.O.Box 11-0236, Beirut, Lebanon. bared@aub.edu.lb
Dardenne
M
M
Kanaan
S A
SA
Atweh
S F
SF
Jabbur
S J
SJ
Saadé
N E
NE
D018712:Analgesics, Non-Narcotic / Q000494:pharmacology; D000818:Animals; D016207:Cytokines / Q000378:metabolism* / Q000502:physiology; D015232:Dinoprostone / Q000378:metabolism* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism* / Q000517:prevention & control; D007106:Immune Sera / Q000494:pharmacology; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000378:metabolism; D008297:Male; D000077239:Meloxicam; D020932:Nerve Growth Factor / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D010146:Pain / Q000517:prevention & control; D010147:Pain Measurement; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000276:immunology / Q000494:pharmacology; D013843:Thiazines / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D013935:Thymic Factor, Circulating / Q000009:adverse effects*; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000187:drug effects / Q000276:immunology / Q000378:metabolism
D018712:Analgesics, Non-Narcotic; D016207:Cytokines; D007106:Immune Sera; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D012795:Sialoglycoproteins; D013843:Thiazines; D013844:Thiazoles; D014409:Tumor Necrosis Factor-alpha; D020932:Nerve Growth Factor; D013935:Thymic Factor, Circulating; D015232:Dinoprostone; D000077239:Meloxicam