Gender differences and inflammation: an in vitro model of blood cells stimulation in prepubescent children

Background: Gender influences clinical presentations and markers in inflammatory diseases. In many chronic conditions, frequency of complications is greater in females, suggesting that continuous inflammatory reaction may induce greater damage in targeted organs and functions. Methods: To investigate gender dimorphism at a cellular level, we evaluated the production of cytokines implicated in inflammatory processes (IL-1, IL-6, PGE-2 and TNF alpha), in healthy prepubescent children of both sex and Turner's syndrome (TS) patients ( genotype XO). We used stimulation by LPS (0.2 and 1 ng/ml) and Pokeweed Mitogen (PWM) on overnight cultures from whole blood samples, collected in 57 subjects: 22 girls/26 boys (5-96 months), and 9 TS patients (6-15 years). The primary outcome was to evaluate if gender influences the production of cytokines, with potential relation to X chromosome monosomy. Secondary endpoints were to relate different cytokines level productions and conditions. Results: We confirm the male over female increased cytokine productions already observed in adults. This is contrasting with numerous observations obtained in vivo about increased production of inflammatory markers in females (CRP, ESR and neutrophil counts), as we recently reported in children. Relative variations of the dimorphism according to stimulus, its concentration and cytokine type are discussed, presenting IL6 with a modulating function that could be more potent in males. TS subjects follow mostly the male pattern of reactivity, sustaining the role of some gene expression differing with X chromosome monosomy and disomy. Conclusions: Persistence of the latter dimorphism throughout life casts doubts on its direct relationship with individual hormonal status, as already documented by others in vitro, and supports the need for alternative hypothesis, such as the influence of X chromosome