Interleukin-1 receptor antagonist, soluble tumor necrosis factor-alpha receptor type I and II, and soluble E-selectin serum levels in multiple sclerosis patients receiving weekly intramuscular injections of interferon-beta1a.
BACKGROUND
interferon beta (IFN-beta) reduces relapse rate and disease progression in patients with the relapsing-remitting form of multiple sclerosis (RRMS). IFN-beta may act by upregulating the expression of anti-inflammatory components of the immune system.


OBJECTIVE
To determine whether weekly intramuscular (i.m.) injection of IFN-beta1a had a short- or long-term effect on the expression of naturally occurring soluble factors that play an immunosuppressive role within the cytokine network.


METHODS
serum levels of interleukin-1 receptor antagonist (IL-1Ra), soluble tumor necrosis factor alpha receptor type I and type II (sTNF-alphaRI and sTNF-alphaRII), and soluble E-selectin (sE-Sel) were followed over time in ten patients with RRMS who were treated with weekly i.m. injections of 30 mg (= 6 MU) of IFN-beta1a. Patient sera were sampled before, and 24, 48, 72, 96, and 168 hours after the first IFN-beta1a injection (short-term), and then at 1, 3, 6, 9 and 12 months after therapy initiation (long-term); highly sensitive, commercially available ELISA tests were used.


RESULTS
serum levels of IL-1Ra, sTNF-alphaRI and sTNF-alphaRII, but not sE-Sel were significantly increased in both short- and long-term follow-up. Interestingly, IL-1Ra, sTNF-alphaRI and sTNF-alphaRII behaviors were completely different, suggesting that these naturally occurring immunoregulatory factors were differentially affected by IFN-beta1a.


CONCLUSIONS
our study demonstrates that weekly i.m. injection of 30 mg of IFN-beta1a induces the expression of soluble mediators that may suppress the activities of pro-inflammatory cytokines such as IL-1 and TNF-alpha.
Perini
P
P
Dept of Neurological & Psychiatrical Sciences, Second Neurological Clinic, University of Padova, School of Medicine, Via E. Vendramini 7, 35137 Padova, Italy.
Tiberio
M
M
Sivieri
S
S
Facchinetti
A
A
Biasi
G
G
Gallo
P
P
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D015703:Antigens, CD / Q000097:blood*; D004334:Drug Administration Schedule; D019040:E-Selectin / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007273:Injections, Intramuscular; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D053590:Interleukin 1 Receptor Antagonist Protein; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012680:Sensitivity and Specificity; D012795:Sialoglycoproteins / Q000097:blood*; D013997:Time Factors
D000276:Adjuvants, Immunologic; D015703:Antigens, CD; D019040:E-Selectin; C507763:IL1RN protein, human; D053590:Interleukin 1 Receptor Antagonist Protein; D017472:Receptors, Interleukin-1; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D047889:Receptors, Tumor Necrosis Factor, Type II; D012795:Sialoglycoproteins; D016899:Interferon-beta; D000068556:Interferon beta-1a