Effects of BCG Vaccination Prior to Specific Immunotherapy on IL-4 / IFN-γ Ratio and AR Total Symptom Score in Persistent Allergic Rhinitis

Efek vaksinasi BCG pre imunoterapi spesifik terhadap rasio IL-4/IFN-γ dan skor gejala total rinitis pada rinitis alergi persisten Latar belakang: Pada penyakit alergi, termasuk rinitis alergi (RA) didominasi oleh respon Th2 yang meningkatkan produksi IL-4 yang kemudian menghambat produksi IFN-. Vaksinasi BCG memicu produksi IL-12 yang menyebabkan pergeseran Th0 ke Th1 dan menginduksi produksi IFN-. Penelitian ini bertujuan untuk membuktikan bahwa vaksinasi BCG pre imunoterapi spesifik (IT) dapat meningkatkan respon IT spesifik selama fase inisial dengan mengukur rasio IL-4/IFN- dan skor gejala total rinitis alergi. Metode: Sebanyak 84 pasien RA persisten sedang–berat yang memenuhi kriteria penelitian dilakukan randomisasi ke dalam 4 kelompok pengobatan (pelarut BCG sebagai kontrol, vaksinasi BCG, IT dan vaksinasi BCG pre IT). Imunoterapi spesifik disuntikkan sub kutan 2 kali seminggu selama 8 minggu dengan ekstrak campuran (D pteronyssinus dan D farinae, 50/50). Vaksinasi BCG diberikan secara intra kutan. Konsentrasi IL-4 dan IFN-γ diukur dari kultur darah segar yang distimulasi phytohemaglutinin (PHA). Rasio IL-4/IFN- dan skor gejala total RA dianalisis sebelum dan setelah IT spesifik 8 minggu. Hasil: Tidak terdapat perbedaan bermakna antara konsentrasi IL-4 dan IFN-γ serta rasionya sebelum dan sesudah terapi pada semua kelompok pengobatan, tetapi rasio IL-4/IFN- pada kelompok BCG pre IT pada akhir fase inisial IT lebih rendah dibanding kelompok IT (p=0,024). Selama fase inisial IT, skor total gejala RA pada kelompok BCG pre IT juga lebih rendah secara bermakna dibanding kelompok IT (p=0,027). Simpulan: Penelitian ini menunjukkan bahwa vaksinasi BCG pre IT meningkatkan respon fase inisial IT spesifik pada penderita rhinitis alergi persisten tanpa efek samping yang berarti. * ENT Department, Faculty of Medicine Diponegoro University-Dr. Kariadi Hospital, Semarang, Jl. Dr. Sutomo 16-18 Semarang Artikel Asli M Med Indones Artikel Asli BCG Vaccination Prior to SIT in Persistent Allergic Rhinitis Volume 43, Nomor 6, Tahun 2009 295 INTRODUCTION Allergic disease is dominated by Th2 responses with increased production of IL-4 resulting in inhibition of IFN- production and induction of IgE production. Allergic rhinitis (AR) may interfere the health status, impair quality of life and need a high cost of treatment. AR prevalence in USA was 14.2%, while in Semarang, Indonesia, the prevalence among 13-14 year old students was 18.6%. Specific immunotherapy (SIT) is an effective treatment for AR and has a long residual effects after discontinuation. The effects of SIT consist of the shift of Th2 to Th1 cytokine production, decrease of the specific IgE and nasal mucosa eosinophils and increase of IgG4 resulting in the decrease of AR symptoms. 6 It is recommended that patients with a moderate to severe persistent AR and are resistant to pharmacologic treatment need a specific immunotherapy. For the last decades, atopic diseases have been increased in the developed countries. The increase might be due to environmental changes, diet factors, the way of life and vaccination programs. There was an inverse association between tuberculin positive response and the low prevalence of atopic diseases in Japan. BCG vaccination decreases an atopic disease since BCG vaccine is a Th1 inducer for the production of endogenous IL-12 cytokine, thus in ducing the IFN- production. IL-12 cytokine also stimulates Th1 and NK cells to produce IFN-. An intranasal BCG infection showed a suppressive effect on eosinophils accumulation within the lung, which is the most pronounced suppressive effect obtained when BCG is given one week before the allergen challenge. The nose and the lung are components of the respiratory tract, however, the effect of BCG in the nasal mucous membrane has not been determined. To test this hypothesis, we have conducted a study to determine production of IL-4 and IFN-γ, IL-4/IFN- ratio, and total symptoms score (TSS) in AR patients given BCG vaccination prior to specific immunotherapy compared to the end of initial phase of specific immunotherapy (SIT).