Differential TNFalpha mRNA regulation detected in the epidermis of leprosy patients.
The epidermis is an important site of the immunoinflammatory response in the skin. In the present study, the expression of cytokine and ICAM-1 (intercellular adhesion molecule-1) genes was evaluated by RT-PCR in the epidermis isolated from biopsies from 25 reactional leprosy patients. TNFalpha and IL-6 mRNAs were detected in all individuals during the reactional state (reversal reaction or erythema nodosum leprosum), IL-8 message was detected in 66.6% and 62.5% of the patients, IL-12 mRNA was present in 91.6% and 62.5% and ICAM-1 in 100% and 71.4%, respectively. In addition, when skin biopsies were obtained from the same patients before and during the reactional episode, an enhancement in cytokine mRNA, but not in ICAM-1 mRNA, was observed. Seven patients were also evaluated at the onset of reaction and during antiinflammatory treatment. In contrast to a preferential decrease in the TNFalpha gene detected in the dermis, during the treatment phase, persistent/enhanced TNFalpha mRNA expression was detected in the epidermis in six out of the seven patients assessed. This peculiar pattern of expression might reflect a differential impact that in vivo antiinflammatory therapy has on the epidermis. The present findings indicate that the epidermis plays an important role in the local inflammatory response in leprosy and that the profile of response detected in the epidermis during the reactions may be regulated differently from that in the dermis.
Teles
Rosane M B
RM
Leprosy Laboratory, Oswaldo Cruz Institute, Fiocruz, Av. Brasil 4365, Manguinhos, Cep 21.045-900, Rio de Janeiro, Brazil.
Moraes
Milton O
MO
Geraldo
Natasha T R
NT
Salles
Ana M
AM
Sarno
Euzenir N
EN
Sampaio
Elizabeth P
EP
D000328:Adult; D000368:Aged; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D020405:Dermis / Q000378:metabolism; D004817:Epidermis / Q000378:metabolism*; D005260:Female; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000378:metabolism; D007917:Leprostatic Agents / Q000627:therapeutic use; D007918:Leprosy / Q000188:drug therapy / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D010431:Pentoxifylline / Q000627:therapeutic use; D011241:Prednisone / Q000627:therapeutic use; D012333:RNA, Messenger / Q000378:metabolism; D013792:Thalidomide / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D007917:Leprostatic Agents; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1; D013792:Thalidomide; D010431:Pentoxifylline; D011241:Prednisone