CYTOKINE NETWORKS WITH INFECTION - MYCOBACTERIAL INFECTIONS, LEISHMANIASIS, HUMAN-IMMUNODEFICIENCY-VIRUS INFECTION, AND SEPSIS

Distinct cytokine profiles are clearly associated with and relate to t he severity of several types of infections. Cytokine networks are appa rent with selected human infectious diseases, such as mycobacterial in fections (leprosy, tuberculosis), the parasitic infection leishmaniasi s, human immunodeficiency virus (HIV) infection, and gram-negative sep sis. Cytokine profiles are determined to some extent by two functional subsets of T lymphocytes, Th1 and Th2. The Th1 cytokines (interferon gamma, interleukin-2 [IL-2], IL-12) enhance cell-mediated immunity, in hibit humoral immunity, and result in protective effect for pathogens that are removed primarily through cell-mediated immunity (Mycobacteri um tuberculosis, Mycobacterium leprae, Leishmania). The Th2 cytokines (IL-4, IL-5, IL-10, IL-13) enhance humoral immunity and inhibit cell-m ediated immunity, and result in protective effect for pathogens remove d primarily through humoral mechanisms. Progression of HIV infection i s associated with a switch from a Th1 to a Th2 profile. For sepsis, un controlled activation of proinflammatory cytokines (IL-1, tumor necros is factor-alpha, interferon-gamma) may be a fundamental defect that pr omotes the detrimental aspects of inflammation, whereas Th2 cytokines may be beneficial in controlling inflammation. Knowledge of basic cyto kine immunopharmacology, networks, and relationships with infectious p rocesses will aid clinicians in determining treatment approaches that are likely to be effective.