[Severe inflammatory disease in children. Rationale for corticosteroid immunomodulating therapy: pathogenic therapy]

Abstract

At the moment it is assumed that each strongly aggressive pathogenic agent, such as bacteria, viruses, toins, trauma, burns, grave asphyxia, allergic agents, and so on, could trigger serious and uncontrollable inflammatory response. That is due to an excessive response of subject's immune system, through the dysregulation of pro-inflammatory cytokines release. The initial physiopathological event of inflammatory response consists in the production of "primary cytokines", TNF-alpha, IL-1 and IL-6 by macrophages. These and other cytokines trigger the progress and amplification of inflammatory process involving secondary mediators and inflammatory cells (Th1/Th2-type cytokines). When the amplification of inflammatory process is excessive ("cytokines storm") a "pro-inflammatory cytokines pathology" can occur and that can determine: 1) systemic inflammatory response syndrome (S.I.R.S.); 2) inflammatory damage of restricted areas (organ pathology). TNF-alpha, IL-1 and IL-6 can act on hypothalamus-hypophisis-surrenal axis and, through cortisol release, can determine a negative feedback on the cytokines gene expression and a physiological anti-inflammatory mechanism. According to our experience we believe that a praecox corticosteroid treatment (Desametasone, Betametasone), in small doses and for a short period, associated with an antibiotic therapy (Ceftazidime, Ceftriaxone, Cefixima, Ceftibuten), could compensate the relative and transitory deficiency of hypothalamus-hypophisis-surrenal axis, and reestablish the physiological control mechanism of cytokines release.