Tumour necrosis factor-alpha (TNF-α) synthesis is associated with the skin and peripheral nerve pathology of leprosy reversal reactions

Abstract

Leprosy may be complicated by episodes of increased cell-mediated immunity towards Mycobacterium leprae (reversal reactions) which result in severe local immunopathology in skin lesions and peripheral nerves. Using in situ hybridization and MoAb techniques we have demonstrated TNF-alpha mRNA and TNF-alpha protein in macrophages infiltrating leprosy skin and peripheral nerve. Levels of TNF-alpha mRNA are significantly increased in reactional skin and nerve, particularly in borderline tuberculoid patients. TNF-alpha mRNA and TNF-alpha protein levels are higher in reactional nerves then reactional skin. In both reactional skin and nerve TNF-alpha mRNA is more abundant than TNF-alpha protein; this may reflect the rapid turnover of TNF-alpha protein in an immunologically dynamic situation, such as is seen in reversal reaction. Our findings emphasize the importance of documenting both mRNA and protein production when assessing the role of cytokines in pathology. The leprosy reversal reaction may be regarded as a useful model of tissue immunopathology in which TNF-alpha is generated as part of the host response to infection, but also produces local tissue damage.

Leprosy type 1 reactions and erythema nodosum leprosum

“…18 Immunohistochemistry studies show greater TNF staining in the skin and nerves during T1Rs compared with non-reactional controls. 19 T1Rs appear to be mediated via Th1 lymphocytes and cells from reactional lesions express the pro-inflammatory cytokines interferon gamma (IFN-γ), interleukin 12 (IL-12) and the oxygen free radical producer inducible nitric oxide synthase. 20 …”

Reactions Following Completion of 1 and 2 Year Multidrug Therapy (MDT)

“…These hypersensitivity reactions occur in roughly onethird of patients with leprosy. Type 1 reactions that occur following a course of antimicrobial therapy are termed RR and are associated with an increasing cellular immune response to mycobacterial antigens, infiltration of reactional sites with interferon-gamma (IFN-γ), 2 tumor necrosis factor-alpha (TNF-α)-secreting CD4 + lymphocytes, 3 and increased cytokine production by peripheral blood lymphocytic cells, 4 resulting in increased levels of serum cytokines 5 . Although RR generally occurs early in the course of effective chemotherapy, these type 1 reactions have been reported as occurring at the time of diagnosis between 3% and 6% of the time by most, 6 whereas others have found these to occur 24% 7 to 28% 8 of the time.…”

Caracterização da dor, da sensibilidade discriminativa e dos achados neuropatológicos na biópsia cutânea em hanseníase em doentes após término do tratamento poliquimioterápico

“…137 . A medida de TNF-alfa sérico antes dos eventos foi preditora para a ocorrência destes, assim como, anormalidades de condução nervosa de fibras sensitivas 137 .…”

“…137 . A medida de TNF-alfa sérico antes dos eventos foi preditora para a ocorrência destes, assim como, anormalidades de condução nervosa de fibras sensitivas 137 . Posteriormente, no estudo INFIR, a quantificação do TNF alfa foi realizada na pele, o TNF alfa foi detectado em 78% das biópsias, a maior detecção ocorreu na forma dimorfa tuberculoide, localizado nos macrófagos e nas células epitelioides no granuloma, e em 7 casos foi detectado em nervos na derme.…”