Lymphatic thoracic duct ligation modulates the serum levels of IL-1beta and IL-10 after intestinal ischemia/reperfusion in rats with the involvement of tumor necrosis factor alpha and nitric oxide.
Intestinal ischemia/reperfusion (I/R) causes local and remote injuries that are multifactorial and essentially inflammatory in nature. To study the putative influences of nitric oxide (NO) and tumor necrosis factor alpha (TNF-alpha) on the release of interleukin (IL) 1beta and IL-10 and the involvement of lymphatic system on a systemic inflammation caused by I/R, we have quantified the serum and lymph levels of IL-1beta and IL-10 in rats during I/R after treatment with inhibitors of NO synthase (N-nitro-L-arginine methyl ester hydrochloride [L-NAME]) or TNF-alpha (pentoxifylline [PTX]). Intestinal I/R was performed by means of a 45-min occlusion of the mesenteric artery, followed by 2-h reperfusion; groups of rats subjected to I/R had the thoracic lymph duct ligated immediately before the procedure. The I/R caused a significant increase of the serum levels of IL-1beta and IL-10 in rats with intact thoracic lymph duct, whereas the thoracic duct ligation blunted the serum release of IL-1beta and elevated that of IL-10. The levels of the cytokines collected in the lymph after I/R increased, and even more increase was observed in L-NAME-treated rats. L-NAME significantly increased the lymph levels of IL-1beta and IL-10; in serum, however, only IL-1beta increased in rats with either intact or ligated thoracic lymph duct. The treatment with PTX reduced the serum levels of IL-1beta irrespective of the lymph circulation interruption but was effective to increase the IL-10 levels in intact rats during I/R. The lymphatic levels of IL-1beta of rats subjected to I/R were reduced and those of IL-10 were increased after treatment with PTX. In conclusion, during I/R, the serum levels of IL-1beta seem modulated by stimulant mechanisms that could be associated with TNF-alpha and inhibited by NO and by the integrity of the thoracic lymphatic flow. On the other hand, IL-10 seems controlled by TNF-alpha-related, largely NO-independent mechanisms. Thus, it is reasonable to suppose that an endogenous mechanism that can limit the systemic inflammatory response ensuing an I/R splanchnic trauma exists.
Cavriani
Gabriela
G
Department of Pharmacology, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Domingos
Helori Vanni
HV
Oliveira-Filho
Ricardo Martins
RM
Sudo-Hayashi
Lia Siguemi
LS
Vargaftig
Bernardo Boris
BB
de Lima
Wothan Tavares
WT
D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016753:Interleukin-10; D053583:Interleukin-1beta / Q000097:blood*; D007422:Intestines; D008026:Ligation; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000097:blood*; D010431:Pentoxifylline / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000097:blood*; D013897:Thoracic Duct; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000097:blood*
D004791:Enzyme Inhibitors; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D009569:Nitric Oxide; D010431:Pentoxifylline; D019331:NG-Nitroarginine Methyl Ester