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

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.

[Histopathological study of the cubital epineurium in patients with undifferentiated forms of Hansen's disease]. / Contribuicão ao estudo histopatolõgico do epineuro cubital em doentes de hanseníse indiferenciada.

Twelve hanseniasis patients, undifferentiated group, with negative bacilloscopy and having undergone no prior treatment, were submitted to a biopsy of the cubial epineurium for histopathological study. All subjects were clinically observed after one month, and six of them were examined 4 to 5 years afterwards. Histopathology of the epineurium presented acid-fast bacilli in one patient and tuberculoid granuloma formation tendency in another. Epineural thickening was observed in nine patients and perivascular lymphomonocuclear inflammatory infiltration in six. The clinical examination after 1 month in the 12 patients as well as after 4 to 5 years in 6 of them, demonstrated innocuousness of the performed biopsy. Four to five years after the initial observation, the clinical examination showed that two patients who remained Mitsuda negative did not present histopathologically thickened epineurium at the beginning, while in four patients who then presented positive Mitsuda, the initial histopathological examination showed epineural thickening. Among the nine patients having a histopathologically thickened epineurium, six did not present initial lesions in the upper limbs. Therefore, the study of the cubital epineurium early thickening deserves special mention, and should be performed in a larger number of patients, as well as in control groups, since the follow-up of four among six patients showed epineural thickening and reversal of the Mitsuda reactions to positivity.

Contribuicao ao estudo histopatologico do epineuro cubital em doentes de hanseniase indiferenciada. / Histopathological study of the cubital epineurium in patients with indifferentiated form of Hansen's disease

Doze doentes de hanseniase, grupo indiferenciado, com baciloscopia negativa e virgens de tratamento, foram submetidos a biopsia de epineuro cubital para estudo histopatologico. Todos os doentes foram observados clinicamente um mes apos, e seis destes puderam ser examinados 4 a 5 anos apos. A histopatologia do epineuro mostrou existencia de bacilos alcool-acido -resistentes em um doente e tendencia a formacao de granuloma tuberculoide em outro. Em nove doentes, pode-se observar espessamento epineural e, em seis, infiltrado inflamatorio linfomononuclear perivascular. O exame clinico apos 1 mes nos 12 doentes e tambem apos 4 a 5 anos em 6 deles demonstrou a inocuidade da biopsia realizada. Quatro a cinco anos apos a observacao inicial, o exame clinico mostrou que dois doentes que permaneciam Mitsuda negativos nao apresentavam epineuro histopatologicamente espessado no inicio, enquanto que em quatro doentes, que passaram a apresentar Mitsuda positivo, o exame histopatologico inicial revelara espessamento epineural. Dos nove doentes que apresentavam epineuro histopatologicamente espessado, seis nao mostravam lesoes iniciais nos membros superiores. O estudo do espessamento precoce do epineuro cubital merece, portanto, especial destaque, devendo ser realizado em maior numero de doentes e em grupo de controle, pois no seguimento de quatro dos seis doentes, observou-se espessamento epineural e viragem da reacao de Mitsuda