The Th1/Th2 cytokine balance changes with the progress of the immunopathological lesion of Sjogren’s syndrome

• Published in: Clinical and experimental immunology Vol. 128; no. 3; pp. 562 - 568
• Main Authors: MITSIAS, D. I., TZIOUFAS, A. G., VEIOPOULOU, C., ZINTZARAS, E., TASSIOS, I. K., KOGOPOULOU, O., MOUTSOPOULOS, H. M., THYPHRONITIS, G.
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01-06-2002; Blackwell; Oxford University Press; Blackwell Science Inc
• Subjects: Biological and medical sciences; Cells, Cultured; Culture Techniques; cytokines; Freezing; Gene Expression; General aspects; Humans; IgE; Immunopathology; Immunophenotyping; Interferon-gamma - biosynthesis; Interferon-gamma - genetics; Interleukin-13 - biosynthesis; Interleukin-13 - genetics; Interleukin-4 - biosynthesis; Interleukin-4 - genetics; Lymphocytes - classification; Lymphocytes - cytology; Lymphocytes - immunology; Medical sciences; Original; RNA, Messenger; Salivary Glands - immunology; Salivary Glands - pathology; Sjogren's Syndrome - immunology; Sjogren's Syndrome - pathology; Sjogren’s syndrome; T lymphocytes; Th1 Cells - immunology; Th1/Th2 balance; Th2 Cells - immunology; Human; Immunopathology; Immune response; Stomatology; Labial gland; IgE; Th1 lymphocyte; Autoimmune disease; Salivary gland; Interleukin 13; Sjögren syndrome; Eye disease; Interleukin 4; Immunological investigation; Systemic disease; T-Lymphocyte; Th2 lymphocyte; Gamma interferon
• ISSN: 0009-9104; 1365-2249
• DOI: 10.1046/j.1365-2249.2002.01869.x

SUMMARY
Expression of type‐1 and type‐2 cytokines at the mRNA level in labial salivary glands (LSG) of patients with Sjogren’s syndrome (SS), as reported by several groups, have generated conflicting results. In the present study we have directly examined the production of IL‐4, IL‐13 and IFN‐γ by lymphocytes infiltrating the LSG of 44 consecutive patients referred for SS evaluation. Cytokines production was evaluated following in vitro culture of LSG in the presence of IL‐2. IFN‐γ
and IL‐13 were detected in the majority of SN (24/44 and 26/44, respectively) while
IL‐4 was present in 5/44 SN. The presence of IFN‐γ was significantly higher in
SS patients, as opposed to patients who did not fulfil the criteria for SS (P
< 0·01). In addition, almost all cultured lymphocytes expressed mRNA for
IFN‐γ (17/19 cultures) and IL‐13 (18/19) while IL‐4 mRNA was also expressed at
high frequency (14/19 cultures). Interestingly, the IFN‐γ mRNA copies in cultured
lymphocytes correlated significantly with the intensity of lymphocytic infiltration
as evaluated by Chisholm’s score (P < 0·01). Furthermore,
RT‐PCR of RNA extracted from whole LSG from 14 SS patients also demonstrated the
presence of all cytokines in the majority of the cases and the prevalence of IFN‐γ
in LSG with high‐grade infiltration. Because IL‐13 was produced by the majority of
the cultured LSG, IgE production was also evaluated. Interestingly, IgE was detected
in 21/44 LSG culture SN and mainly in those biopsies that had Chisholm’s score
less than 0·5 (P < 0·05). We conclude that lymphocytes infiltrating the LSG are capable of producing both Th1 and Th2 cytokines and that the balance between them shifts in favour of Th1 in LSG with high infiltration score and in patients with SS.