Tuberculin reactivity and allergy

Tuberculin, which is an extract of pure culture of the tubercle bacillus, had been developed byRobert Koch in 1891 (1). Initially mistaken as a therapeutic agent believed to provide systemic protection in tuberculosis patients, it became established as a diagnostic tool by Clemens vs. Pirquet (2). He established that reactivity to tuberculin indicates previous infection by the tubercle bacillus. The tuberculin preparation and the skin testing procedure have been modified, but the principle of tuberculin reactivity remains unchanged and is worldwide the standard screening method for tuberculous infection. Mycobacteria elicit a cytokine response which is during successful containment characterized by preferential secretion of Th1-type cytokines both in themurine and in the human immune system (3–5). Similarly, mycobacteria-derived purified protein derivate (PPD) elicits a Th1-type response (3). Conversely, IgE-mediated allergy is characterized by secretion of Th2-type cytokines. Th1-type and Th2-type responses are reciprocally inhibitory (6). A rising trend of allergic diseases has been observed in many countries with a westernized economy (7). The reasons are not fully understood. An attractive explanatory hypothesis relates to a decrease in infections owing to improved hygiene conditions (8). Infections which could theoretically help to explain the observed epidemiological trend include those which induce a persisting Th1-type cytokine pattern and thus provide Th2-inhibitory signals. In this context, a lack of mycobacterial infections and vaccinations has been considered as a particularly potential cause. Mycobacteria don’t belong to the regular human commensal flora, the exposure is thus determined by lifestyle. A possible role of mycobacteria is supported by an extensive body of experimental data which show the capacity of bacille Calmette–Guérin (BCG) or other mycobacteria to mitigate allergic responses to allergens in the murine system (9–15) and epidemiological data demonstrating an inverse association of tuberculosis notification rates and asthma (7, 16). While allergic symptoms or their mediator immunoglobulin (Ig)E as outcome parameters of a Th2-type immune response are relatively easy to measure, tuberculin reactivity has been used as an indicator of effects mediated by the Th1 branch of the immune response. During the last 5 years, several epidemiological studies have addressed a possible association of decreased response to PPD and increased prevalence of allergy. Intriguing results have been reported from a study among Japanese schoolchildren who had been BCGvaccinated repeatedly and who resided in an area with a high tuberculosis prevalence (17). Total IgE values were strongly inverse correlated with the PPD skin test diameter. Moreover, respiratory allergy and eczema as well as allergic sensitization and Th2-type cytokines were less prevalent among child-ren who responded negatively to PPD at 6 and 12 years of age. The distribution of PPD skin test diameters was, however, bimodal and diameters up to >50 mm suggest that not only vaccination with BCG but also mycobacterial infection played a role in this population.No subsequent study has confirmed this strong inverse association of atopy and PPD response. Allergy 2002: 57: 277–280 Printed in UK. All rights reserved Copyright # 2002 Blackwell Munksgaard