We investigated in rats the influence of the lymphatic system and of tumor necrosis factor (TNF) on the lung inflammation resulting from intestinal ischemia/reperfusion (I/R) performed by 45-min occlusion of the superior mesenteric artery followed by 2 h of reperfusion. A group of rats had the thoracic lymph duct ligated before I/R. In lungs, intestinal I/R evoked a significant neutrophil recruitment, and enhanced microvascular permeability, in addition to generation of TNF in serum. In the gut, there was lowered lactate dehydrogenase (LDH) activity and increased microvascular permeability. Upon lymph duct ligation, I/R rats had a significant reduction of pulmonary neutrophil recruitment and plasma extravasation, in addition to high amounts of TNF in the lymph, contrasting with undetectable levels in the serum. In addition, LDH gut levels in these animals were close to basal values; there was also some (yet significant) reduction of microvascular permeability, suggesting that the ligation of the lymphatic duct exerted some degree of protection against the intestinal injury caused by I/R. In I/R rats, the treatment with pentoxifylline (PTX) reduced TNF in serum and blunted other lung alterations. The gut alterations caused by intestinal I/R were largely blocked by PTX. On the other hand, in I/R rats with lymph duct ligation, PTX exacerbated the reduction of pulmonary neutrophil recruitment, but did not affect pulmonary and intestinal microvascular permeabilities. Similarly, intestinal LDH activity and serum TNF levels were unaffected. Overall, our data show that the pulmonary and gut injuries induced by intestinal I/R are partially dependent on TNF, which is conceivably generated in the injured gut tissue due to intestinal I/R and carried by the lymphatic system. Thus, the mesenteric lymphatic drainage seems to play a role as a path modulator of the pulmonary and intestinal dysfunctions that follow a gut trauma.

These findings suggest that variables related to defensive mechanisms, such as lymphocyte recirculation and particles uptake into the lymph nodes can benefit from insulin treatment, whereas glycemic control can benefit transport mechanisms in the lymphatic system, such as lymph flow and lymphatic transport of particles.

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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.