Rheumatic heart disease: proinflammatory cytokines play a role in the progression and maintenance of valvular lesions.
Heart lesions of rheumatic heart disease (RHD) patients contain T-cell clones that recognize heart proteins and streptococcal M peptides. To functionally characterize heart-infiltrating T lymphocytes, we evaluated their cytokine profile, both directly in situ and in T-cell lines derived from the heart (HIL). Interferon (IFN)-gamma, tumor necrosis factor (TNF)-alpha, interleukin (IL)-4, and IL-10 expressions were characterized in 20 heart tissue infiltrates from 14 RHD patients by immunohistochemistry. IFN-gamma-, TNF-alpha-, and IL-10-positive cells were consistently predominant, whereas IL-4 was scarce in the valves. In agreement with these data, the in vitro experiments, in which 13 HILs derived from heart samples of eight patients were stimulated with M5 protein and the immunodominant M5 (81-96) peptide, IL-4 was detected in HIL derived from the atrium (three of six) but not from the valve (zero of seven). IFN-gamma and IL-10 production were detected in culture supernatants in 11 of 13 and 6 of 12 HILs, respectively. The predominant IFN-gamma and TNF-alpha expression in the heart suggests that Th1-type cytokines could mediate RHD. Unlike in reversible myocardium inflammation, the significantly lower IL-4 expression in the valvular tissue (P = 0.02) may contribute to the progression of the RHD leading to permanent valvular damage (relative risk, 4.3; odds ratio, 15.8). The lack of IL-4 in vitro production by valve-derived HIL also emphasizes the more severe tissue destruction in valves observed in RHD.
Guilherme
Luiza
L
Laboratório de Imunologia, Instituto do Coração, HC-FMUSP, Av. Dr. Eneas de Carvalho Aguiar, 44 - 9 andar, São Paulo-SP, 05403-000, Brazil. luizagui@usp.br
Cury
Patricia
P
Demarchi
Lea M F
LM
Coelho
Verônica
V
Abel
Lúcia
L
Lopez
Ana P
AP
Oshiro
Sandra Emiko
SE
Aliotti
Selma
S
Cunha-Neto
Edécio
E
Pomerantzeff
Pablo M A
PM
Tanaka
Ana C
AC
Kalil
Jorge
J
D000293:Adolescent; D000328:Adult; D001011:Aorta / Q000473:pathology; D002469:Cell Separation; D002648:Child; D016207:Cytokines / Q000096:biosynthesis / Q000502:physiology*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006351:Heart Valves / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D007249:Inflammation; D015847:Interleukin-4 / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D010455:Peptides / Q000737:chemistry; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012214:Rheumatic Heart Disease / Q000473:pathology*; D012306:Risk; D013601:T-Lymphocytes / Q000378:metabolism
D016207:Cytokines; D010455:Peptides; D015847:Interleukin-4