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Effect of colchicine on immunoregulatory abnormalities in familial Mediterranean fever
Abstract:
The effect of colchicine on immunoregulatory T lymphocytes in children with familial Mediterranean fever (FMF) was studied. Concanavalin A (Con A)-induced suppressor cell function was significantly (P less than 0.0001) decreased in five untreated FMF patients (15 +/- 3%, mean +/- s.e.) as compared to six age matched paediatric controls (46 +/- 3%) and eight healthy adults (49 +/- 4%). When the five untreated FMF patients' mononuclear cells were pre-incubated in vitro with Con A plus 10(-5) M colchicine, their suppressor cell function was significantly increased (52 +/- 10%, P less than 0.01). Similarly, oral colchicine treatment (0.5 mg twice daily) significantly (P = 0.02) increased the five FMF patients' Con A-induced suppressor cell function to levels (34 +/- 6%) that were not significantly (P greater than 0.05) different than the paediatric controls or the healthy adults. The percentage of OKT8+ cells (but not OKT3+ or OKT4+ cells) was significantly (P less than 0.0001) decreased in 10 untreated FMF patients (16.0 +/- 0.9) as compared to 10 paediatric controls (27.6 +/- 2) or 10 healthy adults (25.7 +/- 0.6). The 10 untreated FMF patients had a significant (P less than 0.002) increase in the OKT4/OKT8 ratio (2.41 +/- 0.13) as compared to 10 FMF patients treated with 0.5 mg twice daily of colchicine (1.81 +/- 0.08), 10 pediatric controls (1.47 +/- 0.2), or 10 healthy adults (1.78 +/- 0.11). Colchicine appears to have corrected the FMF patients' elevated OKT4/OKT8 ratio by both decreasing the percentage of OKT4+ cells and increasing (but only partially correcting) the percentage of OKT8+ cells. Thus FMF patients have a suppressor cell deficiency in which colchicine treatment corrects their deficiency of Con A-induced suppressor cell function and their elevated OKT4/OKT8 ratio. This raises the possibility that colchicine might be potentially useful as an immunomodulating drug in treating patients with autoimmune or allergic diseases associated with a suppressor cell deficiency.
Insights
Familial Mediterranean fever (FMF) patients exhibit reduced suppressor cell function and an elevated OKT4/OKT8 ratio. Colchicine treatment in FMF patients significantly improves suppressor cell activity and normalizes the OKT4/OKT8 ratio, suggesting its potential as an immunomodulator.
Area of Science:
- Immunology
- Pediatrics
- Pharmacology
Background:
- Familial Mediterranean fever (FMF) is an autoinflammatory disorder.
- Patients with FMF exhibit dysregulation of immunoregulatory T lymphocytes.
- A deficiency in suppressor cell function is noted in untreated FMF patients.
Purpose of the Study:
- To investigate the effect of colchicine on immunoregulatory T lymphocytes in children with FMF.
- To assess whether colchicine can correct suppressor cell deficiency and T-cell subset imbalances in FMF.
Main Methods:
- Assessed Concanavalin A (Con A)-induced suppressor cell function in FMF patients and controls.
- Evaluated the effect of in vitro and oral colchicine on suppressor cell function.
- Measured percentages of T-cell subsets (OKT3+, OKT4+, OKT8+) and the OKT4/OKT8 ratio.
Main Results:
- Untreated FMF patients showed significantly decreased Con A-induced suppressor cell function compared to controls.
- In vitro and oral colchicine treatment significantly increased suppressor cell function in FMF patients.
- FMF patients had a decreased percentage of OKT8+ cells and an elevated OKT4/OKT8 ratio, which were partially corrected by colchicine.
Conclusions:
- Colchicine corrects the suppressor cell deficiency and elevated OKT4/OKT8 ratio in FMF patients.
- Colchicine's immunomodulatory effects suggest potential use in autoimmune and allergic diseases linked to suppressor cell deficiency.