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Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12.
Arthritis Rheum. 1999 Sep; 42(9):1967-74.AR

Abstract

OBJECTIVE

To investigate whether immunologic abnormalities in patients with Behçet's disease (BD) are related to abnormalities of the Th1/Th2 ratio.

METHODS

Th1/Th2 cytokine production by peripheral blood lymphocytes (PBL) from 31 patients with BD, 11 patients with inflammatory arthritis, and 10 healthy blood donors was evaluated by intracellular immunofluorescence staining. Serum interleukin-12 (IL-12) levels were measured using an enzyme amplified-sensitivity immunoassay. The effect of recombinant IL-12 (rIL-12) on spontaneous and Fas-mediated apoptosis of phytohemagglutinin (PHA)-stimulated PBL was evaluated by flow cytometry using propidium iodide (PI) staining and a bromodeoxyuridine (BrdU)/PI procedure.

RESULTS

Intracellular immunofluorescence staining of IL-2, IL-4, and interferon-gamma (IFNgamma) in CD3+ lymphocytes from BD patients demonstrated a strong polarization of the immune response toward the Th1 pathway that correlated with the progression of BD. Peripheral Th1 cells were significantly increased in patients with active disease (n = 14) as compared with those in patients in complete remission (n = 17), patients with inflammatory arthritis, and normal donors. In addition, serum IL-12 levels were correlated with peripheral Th1 lymphocytes and disease progression. Apoptotic analysis revealed that PHA-activated PBL from patients with active disease were highly sensitive to spontaneous and Fas-mediated activation-induced cell death. However, addition of rIL-12 to complete medium prevented this spontaneous and Fas-induced apoptosis and enhanced the proliferation of Th1 lymphocytes.

CONCLUSION

Taken together, these results indicate that a strong Th1 immune response occurs in active BD and suggest that IL-12 plays a substantial part in the pathogenesis of BD. By preventing spontaneous and Fas-induced cell death, in fact, it results in an abnormal growth of autoreactive Th1 lymphocytes that could contribute to the prolonged inflammatory autoimmune condition of BD.

Authors+Show Affiliations

University of Bari Medical School, Italy.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10513814

Citation

Frassanito, M A., et al. "Th1 Polarization of the Immune Response in Behçet's Disease: a Putative Pathogenetic Role of Interleukin-12." Arthritis and Rheumatism, vol. 42, no. 9, 1999, pp. 1967-74.
Frassanito MA, Dammacco R, Cafforio P, et al. Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12. Arthritis Rheum. 1999;42(9):1967-74.
Frassanito, M. A., Dammacco, R., Cafforio, P., & Dammacco, F. (1999). Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12. Arthritis and Rheumatism, 42(9), 1967-74.
Frassanito MA, et al. Th1 Polarization of the Immune Response in Behçet's Disease: a Putative Pathogenetic Role of Interleukin-12. Arthritis Rheum. 1999;42(9):1967-74. PubMed PMID: 10513814.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Th1 polarization of the immune response in Behçet's disease: a putative pathogenetic role of interleukin-12. AU - Frassanito,M A, AU - Dammacco,R, AU - Cafforio,P, AU - Dammacco,F, PY - 1999/10/8/pubmed PY - 1999/10/8/medline PY - 1999/10/8/entrez SP - 1967 EP - 74 JF - Arthritis and rheumatism JO - Arthritis Rheum VL - 42 IS - 9 N2 - OBJECTIVE: To investigate whether immunologic abnormalities in patients with Behçet's disease (BD) are related to abnormalities of the Th1/Th2 ratio. METHODS: Th1/Th2 cytokine production by peripheral blood lymphocytes (PBL) from 31 patients with BD, 11 patients with inflammatory arthritis, and 10 healthy blood donors was evaluated by intracellular immunofluorescence staining. Serum interleukin-12 (IL-12) levels were measured using an enzyme amplified-sensitivity immunoassay. The effect of recombinant IL-12 (rIL-12) on spontaneous and Fas-mediated apoptosis of phytohemagglutinin (PHA)-stimulated PBL was evaluated by flow cytometry using propidium iodide (PI) staining and a bromodeoxyuridine (BrdU)/PI procedure. RESULTS: Intracellular immunofluorescence staining of IL-2, IL-4, and interferon-gamma (IFNgamma) in CD3+ lymphocytes from BD patients demonstrated a strong polarization of the immune response toward the Th1 pathway that correlated with the progression of BD. Peripheral Th1 cells were significantly increased in patients with active disease (n = 14) as compared with those in patients in complete remission (n = 17), patients with inflammatory arthritis, and normal donors. In addition, serum IL-12 levels were correlated with peripheral Th1 lymphocytes and disease progression. Apoptotic analysis revealed that PHA-activated PBL from patients with active disease were highly sensitive to spontaneous and Fas-mediated activation-induced cell death. However, addition of rIL-12 to complete medium prevented this spontaneous and Fas-induced apoptosis and enhanced the proliferation of Th1 lymphocytes. CONCLUSION: Taken together, these results indicate that a strong Th1 immune response occurs in active BD and suggest that IL-12 plays a substantial part in the pathogenesis of BD. By preventing spontaneous and Fas-induced cell death, in fact, it results in an abnormal growth of autoreactive Th1 lymphocytes that could contribute to the prolonged inflammatory autoimmune condition of BD. SN - 0004-3591 UR - https://www.unboundmedicine.com/medline/citation/10513814/Th1_polarization_of_the_immune_response_in_Beh��et's_disease:_a_putative_pathogenetic_role_of_interleukin_12_ L2 - https://doi.org/10.1002/1529-0131(199909)42:9<1967::AID-ANR24>3.0.CO;2-Z DB - PRIME DP - Unbound Medicine ER -