Engagement of Posthemorrhagic Shock Mesenteric Lymph on CD4+ T Lymphocytes In Vivo and In Vitro

Background: Immune dysfunction is associated with posthemorrhagic shock mesenteric lymph (PHSML) return. To determine the proliferation and cytokine production capacity of CD4(+) T lymphocytes, the effect of PHSML drainage on spleen CD4(+) T lymphocytes in a mouse model of hemorrhagic shock was assessed. Methods: The normal spleen CD4(+) T lymphocytes were in vitro incubated with either drained normal mesenteric lymph (NML), PHSML during hypotension (PHSML-H), or PHSML from 0 h to 3 h after resuscitation (PHSML-R) to verify direct proliferation effects of PHSML. Results: Hemorrhagic shock led to reduction of proliferation and mRNA expression of interleukin 2 (IL-2) and IL-2 receptor in CD4(+) T lymphocytes and to decrease in IL-2 and interferon gamma (IFN-gamma) levels in supernatants. In contrast, the interleukin-4 levels were increased. These effects were reversed by PHSML drainage. Moreover, NML incubation promoted CD4(+) T lymphocyte proliferation, whereas both PHSML-H and PHSML-R treatment had a biphasic effects on CD4(+) T lymphocyte proliferation, exhibiting an enhanced effect at early stages and an inhibitory effect at later stages. Compared with NML, PHSML-H increased IL-2 expression at 12 h, but decreased expression of both IL-2 and IFN-gamma at 24 h. By contrast, PHSML-R induced significant increases in IL-2 and IFN-gamma levels at 24 h. Interleukin-4 expression in CD4(+) T lymphocytes was reduced at 12 h, but augmented at 24 h after incubation with either PHSML-H or PHSML-R. Conclusions: The results indicate that PHSML has a direct inhibitory effect on CD4(+) T lymphocyte proliferation that induces an inflammatory response, which is associated with cellular immune dysfunction. (C) 2020 Elsevier Inc. All rights reserved.