Immune regulation in children and adults in a community with a high incidence of tuberculosis

[摘要] ENGLISH ABSTRACT: There is a progressive maturation of the immune system from infancy to adulthood. Theimmature immune system in early life is characterised by impaired macrophage functionand antigen presentation as well as a higher naIve to memory T cell ratio with subsequentdiminished IFN-y production. Children with tuberculosis often present withlymphadenopathy, the complications thereof or with systemic spread of the organisms.Adults generally manifest with pronounced systemic effects (such as weight loss and highfever) and immunopathology (such as cavitation and fibrosis). We hypothesised that theimmunopathology in adults may be due to enhanced cytokine production in comparisonto children. The first aim of this study was therefore to measure cytokine responses inhealthy children and adults. Cytokine responses in patients with tuberculosis will beexamined in future studies. Peripheral blood mononuclear cells (PBMC) were isolatedfrom whole blood obtained from 9 healthy children and 9 healthy adults. The cells werecultured in serum-free medium, unstimulated or polyclonally stimulated withPhytohaemagglutinin (PHA). Supernatants were harvested after which IFN-y, IL-2,TNF-a., IL-4 and IL-IO production was determined by means of ELISA analysis. Ri'JAwas ~ubsequently extracted from the cells followed by RT-PCR analysis for the semiquantitativedetermination of mRNA levels of these cytokines. PBMC isolated fromhealthy children produced significantly less IFN-y protein than adults. Futhermore, IFN-yproduction in the adults seemed to be trimodally distributed. No significant differencescould be found in the production of IL-2, TNF-a, IL-4 and IL-] O. Although childrenproduced low levels of IFN-y protein, their IFN-y, TNF-a, IL-2, IL-4 and IL-IO mRNAlevels were comparable to that of adults.Tuberculosis is a major cause of mortality and morbidity, particularly in the third world.Ravensmead and Uitsig, two adjacent suburbs in the Western Cape, have a tuberculosisincidence of> I 000/100000 population. Also, up to 90 % of the children in the WesternCape have been reported to be infested by intestinal parasites such as Ascarislumbricoides and Trichurius trichl/ria. Infection with M tuberculosis indut:es a Th 1Stellenbosch University http://scholar.sun.ac.zaivIn:.,c response, while intestinal parasites elicit a Th2 immune response. Th2dominance induced by intestinal parasite infestations could predispose individuals to anenhanced susceptibility to M. tuberculosis. The second aim of this study was toinvestigate serum IgE levels, surrogate markers for Th2 activation, in the community.The serum 19B levels were subsequently correlated to the tuberculosis incidence perenumerator sub-district (ESD), crowding, female literacy and socio-economic levels. Similarly, the tuberculosis incidence per ESD was correlated with the above mentionedparameters. A significant positive correlation was found between tuberculosis incidenceand the serum 19E levels in the community. However, further studies are needed todetermine if intestinal parasites are the main cause of the high 19B levels in thecommunity and to dCh111ine if parasite loads or Th2 dominance are causally linked to theincidence of tuberculosis. Correlation between serum 19E levels and tuberculosisincidence with the other parameters were significant, except in the case of crowding.The third aim of this study was to measure serum IgE and specific 19E levels againstAscaris and common allergens on presentation of tuberculosis and again after completionof successful treatment. Significant declines in serum 19B and Ascaris specific 19B levelswere observed after completion of tuberculosis treatment. This down regulation of IgElevels may be due to an up regulation of ThI responses in patients following successfultreatment for tuberculosis.

[发布机构] Stellenbosch University