Less Frequent and Less Severe Flu-Like Syndrome in Interferon Beta-1a Treated Multiple Sclerosis Patients with at Least One Allele Bearing the G>C Polymorphism at Position -174 of the IL-6 Promoter Gene.
One of the most common adverse event of interferon beta (IFNβ) therapy for multiple sclerosis is flu-like syndrome (FLS), which has been reportedly related to increased levels of cytokines such as interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-α). Average cytokine levels can be affected by single nucleotide polymorphism in the gene promoter regions. To investigate whether IL-6 -174 G>C and TNF-α -376 G>A polymorphisms could be correlated to the incidence of FLS, and whether an anti-inflammatory/antipyretic therapy may influence FLS development, a prospective observational study was performed in 190 treatment naïve, multiple sclerosis patients who started IM IFNβ-1a 30mcg once weekly. The identification of IL-6 -174 G>C and TNF-α -376 G>A polymorphisms was achieved by performing an amplification-refractory mutation system. Serum IL-6 levels were measured using enzyme-linked immunosorbent assay in blood samples taken before therapy and then after the first and last IFNβ-1a injection of the follow-up. FLS-related symptoms were recorded by patients once per week during the first 12 weeks of therapy into a self-reported diary. We found that patients carrying at least one copy of the C allele at position -174 in the promoter of IL-6 gene produced lower levels of IL-6 and were less prone to develop FLS, which was also less severe. On the contrary, the polymorphism of TNF-α had no effect on FLS. Patients taking the first dose of anti-inflammatory/antipyretic therapy in the peri-injection period (within 1 hour) experienced a reduced FLS severity. In conclusion, the study of IL-6 -174 G>C polymorphism would allow the identification of patients lacking the C nucleotide on both alleles who are at risk of a more severe FLS, and may be addressed to a timely and stronger anti-inflammatory/antipyretic therapy for a more effective FLS prevention.
CREA, Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy.
Diego
D
Bertoli
CREA, Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy.
Federico
F
Serana
CREA, Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy.
Alessandra
A
Sottini
Multiple Sclerosis Center, Spedali Civili of Brescia, Presidio di Montichiari, Brescia, Italy.
Cinzia
C
Cordioli
Department of Neurology, Garibaldi Hospital, Catania, Italy.
Davide
D
Maimone
Department of Neurology, University of Florence-Careggi Hospital, Florence, Italy.
Maria Pia
MP
Amato
Department of Neurosciences Tor Vergata University, S. Lucia Foundation IRCCS, Rome, Italy.
Diego
D
Centonze
Department of Neurology, Ospedale Caldarelli, Napoli, Italy.
Ciro
C
Florio
Biogen Italy, Medical Department, Milan, Italy.
Elisa
E
Puma
Multiple Sclerosis Center, Spedali Civili of Brescia, Presidio di Montichiari, Brescia, Italy.
Ruggero
R
Capra
CREA, Diagnostics Department, Spedali Civili of Brescia, Brescia, Italy.
Luisa
L
Imberti
D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000150:complications* / Q000188:drug therapy; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012140:Respiratory Tract Diseases / Q000175:diagnosis / Q000209:etiology*; D013577:Syndrome; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics; D055815:Young Adult
D000970:Antineoplastic Agents; C508600:IL6 protein, human; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D000068556:Interferon beta-1a