Anti-Inflammatory Drugs Block Cytokine mRNA Accumulation in the Skin and Improve the Clinical Condition of Reactional Leprosy Patients

Abstract

The aim of this study was to investigate in what ways in vivo anti-inflammatory treatment affects cytokine mRNA expression in situ in both erythema nodosum leprosum and reversal reaction patients. Serial biopsies were collected from the patients undergoing leprosy reactions before and during pentoxifylline (n = 7) or thalidomide (n = 3) treatment for erythema nodosum leprosum and prednisone (n = 3) for reversal reaction. Clinical evolution of the skin lesion was assessed during the study and semiquantitative reverse transcription-polymerase chain reaction was used to investigate cytokine mRNA expression at the lesion site. Results showed expression of interferon-gamma, interleukin-6, interleukin-10, interleukin-12 p40, and tumor necrosis factor-alpha in all patients tested at the onset of reactional episodes, but interleukin-4 mRNA was rarely detected in the lesions (n = 4). Follow-up analysis showed that, irrespective of the drugs used, tumor necrosis factor-alpha mRNA was diminished in 10 of the 13 patients tested. A concomitant decrease of mRNA accumulation was also observed for interferon-gamma (nine of 11 patients), interleukin-6 (nine of 11), and interleukin-12 p40 (six of eight). An inhibitory effect on interleukin-10 mRNA was likewise seen after thalidomide and pentoxifylline, but not subsequent to prednisone treatment. The data also demonstrated that cytokine mRNA inhibition correlates to the resolution of the inflammatory response in situ (n = 10), whereas the persistence/enhancement of cytokine message expression after treatment was associated with worsening of the skin condition, as seen in three erythema nodosum leprosum patients whose maintenance of local inflammation was accompanied by the appearance/persistence of interleukin-4 gene expression in situ subsequent to anti-inflammatory treatment. In summary, the participation of cytokines in leprosy inflammatory episodes seems to be directly associated with the patients' clinical evolution following therapy for reaction.

Development of Type 2, But Not Type 1, Leprosy Reactions is Associated with a Severe Reduction of Circulating and In situ Regulatory T-Cells

“…[28][29][30] In addition, IL-6 messenger RNA and protein have been detected in T1R lesions. [31][32][33] Thus, the lack of unequivocal correlations between specific cytokines and distinct phenotypes or outcomes highlights the complexity of the immune response in leprosy. An exception to this could be the high expression of IL-17, which is in agreement with the neutrophil infiltration and Th-17 pattern of immune response that characterize the histological picture of T2R.…”

Anti-inflammatory and antinociceptive activities of an acid fraction of the seeds of Carpotroche brasiliensis (Raddi) (Flacourtiaceae)

“…Common to both types of leprotic reaction are pain and swelling at sites of infection (24) and these reactions are characterized by increased inflammatory activity in nerves and skin lesions that are regulated by the synthesis of cytokines and TNF-α (6,(25)(26)(27).…”

Genetic Polymorphisms of Infectious Diseases in Case-Control Studies

“…For example, there was well-documented evidence that tumor necrosis factor (TNF) was involved in leprosy susceptibility [14] and also in the inflammatory complications along the course of the disease [15,16]. Thus it was a sound possibility to test TNF in a casecontrol study in leprosy, which was done in the first genetic epidemiological population-based study in leprosy that tested the −308 SNP in the promoter region of the TNF gene [17].…”