The immunopharmacology of antileprosy agents

Unlike other acute and chronic bacterial infections, the antimicrobial chemotherapy of leprosy is complex due to the occurrence of adverse immunological reactions.The role played by antimicrobial agents in precipitating or exacerbating these reactions is controversial.Whilst conceding that various mechanisms of induction of adverse immunological reactions exist in this disease, the purpose of this review is to suggest immunopharmacological mechanisms by which chemotherapeutic agents may enhance immune reactivity in individuals with leprosy.To understand these mechanisms by which antimicrobial chemotherapy may contribute to immunolo gically mediated conditions it is necessary to consider the immunological status of untreated individuals with the lepromatous (LL) form of the disease.Immunological status of untreated individuals with LL Acquired specific immunological unresponsiveness (tolerance, anergy) to My cobacterium /eprae antigens is found in individuals with LL and may be total or partial according to the state of advancement of the disease and bacillary load.This specific anergy develops as a consequence of the extremely high antigen load which occurs in LL.Apparently, the high antigen concentrations in vivo reach a threshold at which the host immune system detects that sustained immune reactivity against M. leprae is to the continued detriment of the host.In this situation the immune response is ineffective in eradicating the antigen, but continues to inflict damage on bystander tissues in the vicinity of the antigen.Immunologically mediated tissue damage occurs by the release of toxic oxygen radicals and proteolytic enzymes, such as elastase and collagenase, from phagocytic cells (Figure I) which have been mobilized and activated by pro-inflammatory Iymphokines released from antigen-activated T -lymphocytes.Predisposition to the development of this chronic, ineffective inflammatory response which leads to LL may be genetically determined or acquired (e.g. in nutritional deficiency states).There is no conclusive evidence to indicate the existence of genetic susceptibility to the disease.Induction of 0305-75 1 8/83/054139+06 $0 1 .00