Responses to Ang II (Anciotensin II), Salt Intake, and Lipopolysaccharide Reveal the Diverse Actions of TNF-alpha (Tumor Necrosis Factor-alpha) on Blood Pressure and Renal Function

TNF-alpha (tumor necrosis factor-alpha) is the best known as a proinflammatory cytokine; yet, this cytokine also has important immunomodulatory and regulatory functions. As the effects of TNF-alpha on immune system function were being revealed, the spectrum of its activities appeared in conflict with each other before investigators defined the settings and mechanisms by which TNF-alpha contributed to both host defense and chronic inflammation. These effects reflect self-protective mechanisms that may become harmful when dysregulated. The paradigm of physiological and pathophysiological effects of TNF-alpha has since been uncovered in the lung, colon, and kidney where its role has been identified in pulmonary edema, electrolyte reabsorption, and blood pressure regulation, respectively. Recent studies on the prohypertensive and inflammatory effects of TNF-alpha in the cardiovascular system juxtaposed to those related to NaCl and blood pressure homeostasis, the response of the kidney to lipopolysaccharide, and protection against bacterial infections are helping define the mechanisms by which TNF-alpha modulates distinct functions within the kidney. This review discusses how production of TNF-alpha by renal epithelial cells may contribute to regulatory mechanisms that not only govern electrolyte excretion and blood pressure homeostasis but also maintain the appropriate local hypersalinity environment needed for optimizing the innate immune response to bacterial infections in the kidney. It is possible that the wide range of effects mediated by TNF-alpha may be related to severity of disease, amount of inflammation and TNF-alpha levels, and the specific cell types that produce this cytokine, areas that remain to be investigated further.