T Helper 1/T Helper 2 Cytokine Imbalance in Respiratory Syncytial Virus Infection Is Associated With Increased Endogenous Plasma Cortisol

Abstract

In this study, we demonstrate that during the acute phase of RSV infection, there is an increase in the level of plasma cortisol that is parallel to the decrease in IL-12 and IFN-gamma production. These findings suggest an association between increased plasma cortisol and a decreased Th1-type response. The increase in plasma cortisol was greater in infants with the more severe symptomatology in association with a lower level of IL-12 and IFN-gamma production. The potential causative role of endogenous cortisol in the imbalance of the Th1/Th2 response observed during severe RSV infection requires additional investigation. Our results suggest that the immunologic changes observed in the more severely ill patients may be partially explained by the increased levels of plasma cortisol. This finding should be taken into consideration when systemic steroids are prescribed to infants infected with the RSV because there is still controversy regarding the efficacy of systemic steroid use in severe bronchiolitis.

Mucosal inoculation with an attenuated mouse pneumovirus strain protects against virulent challenge in wild type and interferon-gamma receptor deficient mice

“…The role of IFNγ has also been explored in the HRSV mouse challenge model [47][48][49] and has been detected in lung tissue in response to acute infection with virulent PVM J3666 [50; Table 3]. IFNγ has also been associated with a "Th1/ Th2 imbalance" [51,52], and has been implicated in a variety of pathologic outcomes related to hRSV infection, including prolonged respiratory dysfunction [53], and the exaggerated inflammatory response to an earlier parenteral vaccine formulation [54,55]. The IFNγR−/− mice used in this study, originally developed by Huang and colleagues [56] have a phenotypically normal immune system, but when challenged, demonstrate increased susceptibility to vaccinia virus, listeria and mycobacteria species despite normal cytotoxic and T helper cell responses.…”

The role of Th17 and Treg responses in the pathogenesis of RSV infection

“…However, the Th1/Th2 balance, as explanatory model for the pathogenesis of the RSV infection, is not absolute and has been contradicted by several human studies in which a Th2 predominance (21)(22)(23)(24)(25) and/or a decreased Th1 response (22,23,25) were not confirmed, implying that different mechanisms are involved in the immune-mediated events during severe RSV bronchiolitis.…”

Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

“…25 During infections, otherwise healthy as well as malnourished individuals may experience high ACTH-induced plasma cortisol levels. [26][27][28][29][30][31] During severe infection, these levels may be equivalent to prednisolone concentrations following a single dose of 20 mg/m 2 in children with ALL. Here, the median peak level is 221 ng/ml, which corresponds to 613 nM prednisolone or 2453 nM cortisol, given an equipotency of 1:4.…”

“…28,45 At birth, humoral and cellular immunity, the Th1/Th2 balance and the hypothalamus-pituitary-adrenal axis are relatively Table 1 Under 5-year mortality rate a and incidence of acute lymphoblastic leukemia by age groups b For some countries, only regional data on ALL incidence are available.…”

“…48 Cortisol favors the production of the anti-inflammatory Th2 cytokines such as IL-4 and IL-10 (an IL-12 inhibitor), and can prevent the damaging and proliferative stress of the proinflammatory Th1 cytokines by acting directly on T cells or indirectly by inhibiting IL-12 production by monocytes. 28,49 Although it remains to be proven in humans, animal models have shown that intense stimulation of the immune system early in life with Gram-negative bacterial endotoxins induces permanent changes in the immune response with subsequent more sustained rises in plasma cortisol at later stress and more suppression of lymphocyte proliferation. 50 The adrenal hypothesis proposes qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that explain several of the observations on which Alexander Kinlen 43 and Mel Greaves 44 have founded their etiological hypotheses on childhood ALL.…”