transforming-growth-factor-beta and Heat-Stroke

The online version contains supplementary material available at 10.1007/s00531-022-02219-9.

Topics: Accidents, Occupational; Adult; Animals; Anxiety; beta Catenin; Chromatography, High Pressure Liquid; Chronic Disease; Cities; Depression; Drugs, Chinese Herbal; Flavonoids; Heat Stroke; Hesperidin; Humans; Hyperplasia; Hypoxia-Inducible Factor 1, alpha Subunit; Interleukin-10; Interleukin-6; Kruppel-Like Factor 4; Macrophages, Alveolar; Medical Staff; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Occupational Health; Occupational Injuries; Occupational Stress; Occupations; PPAR gamma; Pulmonary Fibrosis; RNA, Messenger; Sanitation; Silicon Dioxide; Sinusitis; Stress, Psychological; Surveys and Questionnaires; Transforming Growth Factor beta; Tumor Necrosis Factor-alpha; X-Box Binding Protein 1; Young Adult

We have demonstrated that therapeutic administration of L-arginine (L-arg) (120 mg/kg) at +2 h of whole body hyperthermia (WBH) could rescue the mice from heatstroke-induced death. Studies were undertaken to elucidate the role of L-arg in the immunomodulation of the heat-stressed mice. Administration of L-arginine (L-arg), (120 mg/kg, i.p.), at +2 h of WBH, rescued the mice from heat-induced death and reduced the hypothermia. At +4 and +24 h of WBH, levels of IL-1beta, IFN-gamma, nitrite, TNF-alpha, IL-4, TGF-beta1, inducible form of nitric oxide synthase (iNOS), and corticosterone significantly increased compared to the sham group. The elevated levels of Th(1) cytokines, namely TNF-alpha, IL-1beta, IFN-gamma, nitrite, and iNOS, decreased significantly both at +4 and +24 h of WBH, following L-arg administration. However, L-arg administration did not reduce the increased levels of Th(2) cytokines, namely IL-4 and TGF-beta1, in WBH mice at +4 h of WBH. L-arg administration significantly increased the levels of Th(2) cytokines at +24 h of WBH, compared to the saline-treated WBH mice. L-arg administration significantly increased both the splenic and hepatic arginase activity at +4 and +24 h of WBH compared to the saline-treated WBH mice. L-NAME treatment at +2 h of WBH and anti-TGF-beta antibody treatment at 0 h of WBH significantly increased the mortality compared to the saline-treated WBH mice. Altered liver histopathology was attenuated following the administration of L-arg at +2 h of WBH. These results suggest that therapeutic administration of L-arg at appropriate concentration and time attenuates the acute inflammatory response, leading to the rescue of mice from heatstroke.

Topics: Animals; Antibodies; Arginine; Corticosterone; Cytokines; Dexamethasone; Heat Stroke; Liver; Mice; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase Type II; Nitrites; Th1 Cells; Th2 Cells; Transforming Growth Factor beta