Abstract
Activation of the interferon (IFN) system is an early defence mechanism against viral infections. The virus stimulates production of IFN by nucleated cells including the peripheral blood mononuclear cells (PBMC), and this IFN in turn activates several IFN-dependent immune mechanisms including the induction of an anti-viral state in cells, which prevents or retards further intracellular viral replication. In an ongoing study of 1,500 individuals of all ages and with various illnesses, we found 15 cases (representing 5% of patients with acute viral disease) in whom the IFN system response during an acute viral illness was absent or grossly deficient. There was no detectable IFN in the blood, PBMC did not produce IFN-alpha and IFN-gamma or produced minimal amounts of one of them in vitro following appropriate stimulation, and the patients' PBMC were not in an anti-viral state. These patients had severe progressive or fulminant viral disease, often ending fatally. IFN therapy appears to be beneficial in these cases, as it rapidly induced a cellular antiviral state in most cases, stimulated in vitro IFN-alpha and IFN-gamma production by PBMC, and led to rapid recovery in seven of the nine patients who received treatment for at least 3 days. In our opinion IFN replacement therapy should be commenced as early as possible in such cases, and before irreversible cell and organ damage occur.
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- Chadda H., Brenner M. K., Valman H. B., Webster A. D. Production of leucocyte interferon in vitro in children with recurrent respiratory infections. Lancet. 1984 Jun 2;1(8388):1247–1247. doi: 10.1016/s0140-6736(84)91738-0. [DOI] [PubMed] [Google Scholar]
- Epstein L. B., Ammann A. J. Evaluation of T lymphocyte effector function in immunodeficiency diseases: abnormality in mitogen-stimulated interferon in patients with selective IgA deficiency. J Immunol. 1974 Feb;112(2):617–626. [PubMed] [Google Scholar]
- Hahn T., Levin S., Handzel Z. T. Production of immune and viral interferon by lymphocytes of newborn infants. Isr J Med Sci. 1980 Jan;16(1):33–36. [PubMed] [Google Scholar]
- Hahn T., Levin S. The interferon system in patients with malignant disease. J Interferon Res. 1982;2(1):97–102. doi: 10.1089/jir.1982.2.97. [DOI] [PubMed] [Google Scholar]
- ISAACS A., LINDENMANN J. Virus interference. I. The interferon. Proc R Soc Lond B Biol Sci. 1957 Sep 12;147(927):258–267. doi: 10.1098/rspb.1957.0048. [DOI] [PubMed] [Google Scholar]
- Isaacs D., Clarke J. R., Tyrrell D. A., Webster A. D., Valman H. B. Deficient production of leucocyte interferon (interferon-alpha) in vitro and in vivo in children with recurrent respiratory tract infections. Lancet. 1981 Oct 31;2(8253):950–952. doi: 10.1016/s0140-6736(81)91153-3. [DOI] [PubMed] [Google Scholar]
- Levin S., Hahn T. Evaluation of the human interferon system in viral disease. Clin Exp Immunol. 1981 Dec;46(3):475–483. [PMC free article] [PubMed] [Google Scholar]
- Levin S., Hahn T. Interferon system in acute viral hepatitis. Lancet. 1982 Mar 13;1(8272):592–594. doi: 10.1016/s0140-6736(82)91751-2. [DOI] [PubMed] [Google Scholar]
- Levin S., Hahn T., Rosenberg H., Bino T. Treatment of life-threatening viral infections with interferon alpha: pharmacokinetic studies in a clinical trial. Isr J Med Sci. 1982 Apr;18(4):439–446. [PubMed] [Google Scholar]
- Levin S., Schlesinger M., Handzel Z., Hahn T., Altman Y., Czernobilsky B., Boss J. Thymic deficiency in Down's syndrome. Pediatrics. 1979 Jan;63(1):80–87. [PubMed] [Google Scholar]
- Ludwig H. Absent serum interferon in chronic lymphatic leukemia. N Engl J Med. 1979 Nov 1;301(18):1007–1007. doi: 10.1056/NEJM197911013011821. [DOI] [PubMed] [Google Scholar]
- Miller M. E., Hummeler K. Thymic dysplasia ("Swiss agammaglobulinemia"). II. Morphologic and functional observations. J Pediatr. 1967 May;70(5):737–744. doi: 10.1016/s0022-3476(67)80324-x. [DOI] [PubMed] [Google Scholar]
- Neighbour P. A., Bloom B. R. Absence of virus-induced lymphocyte suppression and interferon production in multiple sclerosis. Proc Natl Acad Sci U S A. 1979 Jan;76(1):476–480. doi: 10.1073/pnas.76.1.476. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Neighbour P. A., Grayzel A. I. Interferon production of vitro by leucocytes from patients with systemic lupus erythematosus and rheumatoid arthritis. Clin Exp Immunol. 1981 Sep;45(3):576–582. [PMC free article] [PubMed] [Google Scholar]
- Pedersen-Bjergaard J., Haahr S., Philip P., Thomsen M., Jensen G., Ersbøll J., Nissen N. I. Abolished production of interferon by leucocytes of patients with the acquired cytogenetic abnormalities 5q -- or -- 5 in secondary and de-novo acute non-lymphocytic leukaemia. Br J Haematol. 1980 Oct;46(2):211–223. doi: 10.1111/j.1365-2141.1980.tb05960.x. [DOI] [PubMed] [Google Scholar]
- Ray C. G., Davis S. D. Leucocyte interferon production in immunological deficiency diseases. Lancet. 1970 Feb 7;1(7641):312–312. doi: 10.1016/s0140-6736(70)90692-6. [DOI] [PubMed] [Google Scholar]
- Strander H., Cantell K., Leisti J., Nikkila E. Interferon response of lymphocytes in disorders with decreased resistance to infections. Clin Exp Immunol. 1970 Feb;6(2):263–272. [PMC free article] [PubMed] [Google Scholar]
- Virelizier J. L., Griscelli C. Défaut sélectif de sécrétion d'interféron associé à un déficit d'activité cytotoxique naturelle. Arch Fr Pediatr. 1981 Feb;38(2):77–81. [PubMed] [Google Scholar]
- Virelizier J. L., Lenoir G., Griscelli C. Persistent Epstein-Barr virus infection in a child with hypergammaglobulinaemia and immunoblastic proliferation associated with a selective defect in immune interferon secretion. Lancet. 1978 Jul 29;2(8083):231–234. doi: 10.1016/s0140-6736(78)91744-0. [DOI] [PubMed] [Google Scholar]
- Wallach D. Quantification of the antiviral effect of interferon by immunoassay of vesicular stomatitis virus proteins. J Gen Virol. 1983 Oct;64(Pt 10):2221–2227. doi: 10.1099/0022-1317-64-10-2221. [DOI] [PubMed] [Google Scholar]