The immunoregulatory abilities of polymorphonuclear neutrophils in the course of multiple sclerosis

Abstract

THE p olym or ph on uclear n eutr op h ils (PMN) po s s e s s s ufficie n t p ote ntial to affect both im m un e r es p o ns e an d in flam m ation , h o w e ver it h as no t been yet de s cribed in th e co urs e of m ultip le s cler o s is (MS). IntroductionMultiple sclerosis (MS) is a dise as e in w hich multifoc al inflammation and damage of the blood -brain barrier and myelin sheath are salie nt pathologic features. Overw he lming evidenc e demons trates that MS is a pre dominantly T-c ell and monoc yte/mac rophageme diated autoimmune disorde r.1 ,2 Polymorphonuclear ne utrop hils (PMN) have not be en considere d as a ce ll population participating in it.3 PMN can how e ver ex pre ss immunore gulatory abilities, that has not be en ye t de sc ribe d in the c ourse of MS. Activated in vitro PMN produc e a numbe r of immune mediators including cytokines like IL-1b , IL-4, IL-6, IL-8, IL-10, IL-12, TNF, TGF-b 1. 4 ,5 There fore the re gulatory functions of these ce lls may be postulate d in the c ourse of MS. PMN in the pe ripheral blood (PB) of MS patients can be primed mainly by inflammatory cytokine s like IL-1, INF-g , or by TNF-a sec re te d by mononuclear ce lls. Hypothetically PMN priming or activation in PB of MS patients may dep end also on compleme nt (especially C5a) immunologic al c omplex es, or certain me tabolite s of the arachidonic ac id (LTB 4 , PAF).Priming re sults in the enhanced ex p re ssion on PMN of re cep tors for chemokines and other chemotactic pep tide s, 6 priming also enhance s the ex pre ssion of CD11b/CD18 molecules on PMN c ell surface 7,8 w hich re sults in the indire ct ac tivation of PMN.9,10 In the pre sente d pap er w e have suggeste d that PMN priming can be obse rved in MS patie nts p eriphe ral blood. Patients and methodsPatients (34 total; 19 w omen and 15 men, aged 22-56 years) w ere se lecte d w ith a clinic ally definitive diagnosis of MS 1 1 and w ith Kurtzke Ex panded Disability Status Scale 12 scores 5 or few er and categorized as having the re lapsing-re mitting MS (RR-MS) course for at least 5 years but curre ntly in re mission (REM) (n =13), as having either sec ondary CP-MS for at least 2 ye ars (n =13) or RR-MS and currently ex pe riencing clinical ex ace rbation (REL) of the disease (n = 12). Ex acerbations w ere defined as the appearance of new symptoms or significant w orsening of the old ones, attributabl e to MS, for at least 24 hours w ithout any fever.The control group c onsiste d of patients w ith other ne urologic al diseas es (OND) (14 total; nine w omen and five men, aged from 24 to 37 ye ars), including those w ith vasomotor headache (n = 8) and ischialgia (n = 6). Sample collectionThe studies w e re performed on PMN of the p eripheral venous blood, c ollec te d into heparin-containin g tubes (10 U/ml).0962-9351/98/050335-04 $9.00 © 1998 Carfax Publishing Ltd 335 Research PaperMediators of Inflammation, 7, 335-338 (1998) TNF labelling with fluorescein isothiocyanate (FITC)The synthesis and biological analysis of the TNF molecules w ere pe rfor...

Gestational bisphenol-A exposure lowers the threshold for autoimmunity in a model of multiple sclerosis

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Inhibition of myeloperoxidase at the peak of experimental autoimmune encephalomyelitis restores blood–brain barrier integrity and ameliorates disease severity

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