The role of the Th-1 to Th-2 shift of the cytokine profiles of CD4 helper cells in the pathogenesis of autoimmune and hypercatabolic diseases

Abstract The task of the immune system is the continuous elimination of endogenous cellular debris and the elimination, when necessary, of exogenous structures. It therefore seems useful and practical to add to the paradigms ‘self’ and ‘not self’ the term ‘altered self’. The concept of stress, introduced by W. B. Cannon and H. Selye in the 1930s, covers the wide range of aggressive environmental influences which for their part result in a uniform shift of the metabolism in the direction of catabolism. This results from the activation of the neuroendocrine stress axis, hypothalamus-pituitary-adrenals, and causes an increased release of catecholamines and glucocorticoids. These latter substances limit life-threatening acute-phase reactions by endogenous inflammation mediators. The purpose of the shift of the cytokine profiles of the CD4 lymphocytes from Th-1 to Th-2 is, with the return of a raised cortisol level to normal values, to temporarily take over the anti-inflammatory functions of the cortisol. A sustained Th-2 shift is an expression of a persistent hypercortisolism in autoimmune states. The suppression of the anti-inflammatory effects of cortisol as a result of states of excessive stress leads to hypercatabolic diseases such as AIDS, sepsis and toxic shock syndrome and protein calorie malnutrition (NAIDS). In the prevention and treatment of AIDS and NAIDS, besides the elimination of the causes of stress, the prophylactic and therapeutic efforts are based mainly on the activation of the mesenchymal production of anabolic matrix components, mainly glycosaminoglycans, and the neutralization of OZ and NO radicals and inflammation mediators from macrophages by polyanions and polyphenols. In our opinion, in sepsis and toxic shock syndromes, lasting reduction of the mortality rates for these diseases is best achieved through the early administration of high intravenous doses of gammaglobulins.