Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Clinical Reviews in Allergy & Immunology
Published in: Clinical Reviews in Allergy & Immunology 1/2010

01-02-2010

Use of Cytokine Therapy in Primary Immunodeficiency

Authors: Sumita Roy-Ghanta, Jordan S. Orange

Published in: Clinical Reviews in Allergy & Immunology | Issue 1/2010

Login to get access

Abstract

Of the six cytokine therapies approved by the US Food and Drug Administration, five of them have been used in patients with primary immunodeficiency (PID). In some applications, clear benefits have been demonstrated, while in others, effects have been more marginal. The most compelling current applications of cytokine therapy in PID are those of granulocyte colony stimulating factor in severe congenital neutropenia and interferon gamma in chronic granulomatous disease. Despite encouraging results with interleukin-2 in common variable immunodeficiency and select other indications, its use in PID is not widespread.
Literature
1.
Zsebo KM, Cohen AM et al (1986) Recombinant human granulocyte colony stimulating factor: molecular and biological characterization. Immunobiology 172(3–5):175–184PubMed
2.
Metcalf D (1997) The molecular control of granulocytes and macrophages. Ciba Found Symp 204:40–50; discussion 50–46PubMed
3.
Schroder K, Hertzog PJ et al (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75(2):163–189CrossRefPubMed
4.
Thitinan S, McConville JT (2009) Interferon alpha delivery systems for the treatment of hepatitis C. Int J Pharm 369:121–135CrossRefPubMed
5.
Smith KA, Favata MF et al (1983) Production and characterization of monoclonal antibodies to human interleukin 2: strategy and tactics. J Immunol 131(4):1808–1815PubMed
6.
Wriedt K, Kauder E et al (1970) Defective myelopoiesis in congenital neutropenia. N Engl J Med 283(20):1072–1077PubMed
7.
Weston B, Todd RF 3rd et al (1991) Severe congenital neutropenia: clinical effects and neutrophil function during treatment with granulocyte colony-stimulating factor. J Lab Clin Med 117(4):282–290PubMed
8.
Welte K, Zeidler C et al (1990) Differential effects of granulocyte-macrophage colony-stimulating factor and granulocyte colony-stimulating factor in children with severe congenital neutropenia. Blood 75(5):1056–1063PubMed
9.
Boxer LA, Hutchinson R et al (1992) Recombinant human granulocyte-colony-stimulating factor in the treatment of patients with neutropenia. Clin Immunol Immunopathol 62(1 Pt 2):S39–S46CrossRefPubMed
10.
Dale DC, Bonilla MA et al (1993) A randomized controlled phase III trial of recombinant human granulocyte colony-stimulating factor (filgrastim) for treatment of severe chronic neutropenia. Blood 81(10):2496–2502PubMed
11.
Kostmann R (1956) Infantile genetic agranulocytosis; agranulocytosis infantilis hereditaria. Acta Paediatr Suppl 45(Suppl 105):1–78PubMed
12.
Germeshausen M, Grudzien M et al (2008) Novel HAX1 mutations in patients with severe congenital neutropenia reveal isoform-dependent genotype–phenotype associations. Blood 111(10):4954–4957CrossRefPubMed
13.
Bonilla MA, Gillio AP et al (1989) Effects of recombinant human granulocyte colony-stimulating factor on neutropenia in patients with congenital agranulocytosis. N Engl J Med 320(24):1574–1580PubMed
14.
Page AR, Good RA (1957) Studies on cyclic neutropenia; a clinical and experimental investigation. AMA J Dis Child 94(6):623–661PubMed
15.
Guerry DT, Dale DC et al (1973) Periodic hematopoiesis in human cyclic neutropenia. J Clin Invest 52(12):3220–3230CrossRef
16.
Wright DG, Dale DC et al (1981) Human cyclic neutropenia: clinical review and long-term follow-up of patients. Medicine (Baltimore) 60(1):1–13CrossRef
17.
18.
Hammond H, Price TH et al (1989) Treatment of cyclic neutropenia with granulocyte colony-stimulating factor. N Engl J Med 320(20):1306–1311PubMed
19.
Hanada T, Ono I et al (1990) Childhood cyclic neutropenia treated with recombinant human granulocyte colony stimulating factor. Br J Haematol 75(1):135–137CrossRefPubMed
20.
Hord JD, Whitlock JA et al (1997) Clinical features of myelokathexis and treatment with hematopoietic cytokines: a case report of two patients and review of the literature. J Pediatr Hematol Oncol 19(5):443–448CrossRefPubMed
21.
Wetzler M, Talpaz M et al (1990) A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia. Am J Med 89(5):663–672CrossRefPubMed
22.
Wetzler M, Talpaz M et al (1992) Myelokathexis: normalization of neutrophil counts and morphology by GM-CSF. JAMA 267(16):2179–2180CrossRefPubMed
23.
Diaz GA (2005) CXCR4 mutations in WHIM syndrome: a misguided immune system? Immunol Rev 203:235–243CrossRefPubMed
24.
Cernelc P, Andoljsek D et al (2000) Effects of molgramostim, filgrastim and lenograstim in the treatment of myelokathexis. Pflugers Arch 440(5 Suppl):R81–R82CrossRefPubMed
25.
26.
Winkelstein JA, Marino MC et al (2003) The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients. Medicine (Baltimore) 82(6):373–384CrossRef
27.
Ostenstad B, Giliani S et al (1997) A boy with X-linked hyper-IgM syndrome and natural killer cell deficiency. Clin Exp Immunol 107(2):230–234CrossRefPubMed
28.
Wang WC, Cordoba J et al (1994) Successful treatment of neutropenia in the hyper-immunoglobulin M syndrome with granulocyte colony-stimulating factor. Am J Pediatr Hematol Oncol 16(2):160–163PubMed
29.
Simon G, Marodi L (1995) Successful treatment of cyclic neutropenia associated with hyperimmunoglobulin M syndrome using recombinant granulocyte-colony stimulating factor. Orv Hetil 136(40):2169–2172PubMed
30.
Jacobs ZD, Guajardo JR et al (2008) XLA-associated neutropenia treatment: a case report and review of the literature. J Pediatr Hematol Oncol 30(8):631–634CrossRefPubMed
31.
Segal AW (1987) Absence of both cytochrome b-245 subunits from neutrophils in X-linked chronic granulomatous disease. Nature 326(6108):88–91CrossRefPubMed
32.
Muhlebach TJ, Feickert HJ et al (1991) Granulocyte-macrophage colony stimulating factor does not improve neutrophil oxidative metabolism in a patient with variant X-linked chronic granulomatous disease. Eur J Pediatr 150(8):575–578CrossRefPubMed
33.
Nichols KE, Ma CS et al (2005) Molecular and cellular pathogenesis of X-linked lymphoproliferative disease. Immunol Rev 203:180–199CrossRefPubMed
34.
Strnad-Trojan N, Linde R et al (2006) Treatment of HCV infection with interferon alpha-2b and ribavirin in a patient with X-linked lymphoproliferative syndrome. Eur J Pediatr 165(5):348–350CrossRefPubMed
35.
Foruny JR, Barcena R et al (2006) Benefit of pegylated interferon-alpha-2a/ribavirin in a patient with common variable immunodeficiency and hepatitis C virus cirrhosis after liver transplantation and splenic embolization. Transplantation 82(2):289–290CrossRefPubMed
36.
Bohm M, Luger TA et al (2008) Disseminated giant molluscum contagiosum in a patient with idiopathic CD4+ lymphocytopenia. Successful eradication with systemic interferon. Dermatology 217(3):196–198CrossRefPubMed
37.
Freeman AF, Holland SM (2008) The hyper-IgE syndromes. Immunol Allergy Clin North Am 28(2):277–291, viiiCrossRefPubMed
38.
Kilic SS, Kilicbay F (2006) Interferon-alpha treatment of molluscum contagiosum in a patient with hyperimmunoglobulin E syndrome. Pediatrics 117(6):e1253–e1255CrossRefPubMed
39.
Ozarmagan G, Didem Yazganoglu K et al (2005) Hyper-IgE syndrome with widespread premalign oral papillomas treated with interferon alpha2b. Acta Derm Venereol 85(5):433–435CrossRefPubMed
40.
Souillet G, Rousset F et al (1989) Alpha-interferon treatment of patient with hyper IgE syndrome. Lancet 1(8651):1384CrossRefPubMed
41.
Benninghoff U, Cattaneo F et al (2008) Clinical improvement and normalized Th1 cytokine profile in early and long-term interferon-alpha treatment in a suspected case of hyper-IgE syndrome. Pediatr Allergy Immunol 19(6):564–568CrossRefPubMed
42.
Fuentes-Paez G, Saornil MA et al (2007) CHARGE association, hyper-immunoglobulin M syndrome, and conjunctival MALT lymphoma. Cornea 26(7):864–867CrossRefPubMed
43.
Shiroma N, Omi T et al (2004) A case of X-linked agammaglobulinemia with progressive encephalitis. Pediatr Neurol 31(5):371–373CrossRefPubMed
44.
King CL, Gallin JI et al (1989) Regulation of immunoglobulin production in hyperimmunoglobulin E recurrent-infection syndrome by interferon gamma. Proc Natl Acad Sci U S A 86(24):10085–10089CrossRefPubMed
45.
Aihara Y, Mori M et al (1998) Recombinant IFN-gamma treatment of a patient with hyperimmunoglobulin E syndrome triggered autoimmune thrombocytopenia. J Interferon Cytokine Res 18(8):561–563CrossRefPubMed
46.
Metin A, Uysal G et al (2004) Tuberculous brain abscess in a patient with hyper IgE syndrome. Pediatr Int 46(1):97–100CrossRefPubMed
47.
Pung YH, Vetro SW et al (1993) Use of interferons in atopic (IgE-mediated) diseases. Ann Allergy 71(3):234–238PubMed
48.
Bemiller LS, Roberts DH et al (1995) Safety and effectiveness of long-term interferon gamma therapy in patients with chronic granulomatous disease. Blood Cells Mol Dis 21(3):239–247CrossRefPubMed
49.
Weening RS, Leitz GJ et al (1995) Recombinant human interferon-gamma in patients with chronic granulomatous disease–European follow up study. Eur J Pediatr 154(4):295–298PubMed
50.
The International Chronic Granulomatous Disease Cooperative Study Group (1991) A controlled trial of interferon gamma to prevent infection in chronic granulomatous disease. N Engl J Med 324(8):509–516
51.
Marciano BE, Wesley R et al (2004) Long-term interferon-gamma therapy for patients with chronic granulomatous disease. Clin Infect Dis 39(5):692–699CrossRefPubMed
52.
Woodman RC, Erickson RW et al (1992) Prolonged recombinant interferon-gamma therapy in chronic granulomatous disease: evidence against enhanced neutrophil oxidase activity. Blood 79(6):1558–1562PubMed
53.
Muhlebach TJ, Gabay J et al (1992) Treatment of patients with chronic granulomatous disease with recombinant human interferon-gamma does not improve neutrophil oxidative metabolism, cytochrome b558 content or levels of four anti-microbial proteins. Clin Exp Immunol 88(2):203–206PubMed
54.
Kantar A, Oggiano N et al (1994) Successful interferon gamma therapy in a patient with X-linked chronic granulomatous disease. McLeod syndrome and hyper-IgE. Case report. Minerva Pediatr 46(4):157–160PubMed
55.
Ezekowitz RA, Dinauer MC et al (1988) Partial correction of the phagocyte defect in patients with X-linked chronic granulomatous disease by subcutaneous interferon gamma. N Engl J Med 319(3):146–151PubMedCrossRef
56.
Condino-Neto A, Newburger PE (2000) Interferon-gamma improves splicing efficiency of CYBB gene transcripts in an interferon-responsive variant of chronic granulomatous disease due to a splice site consensus region mutation. Blood 95(11):3548–3554PubMed
57.
Marchand I, Mahe E et al (2008) Disseminated BCG infection revealing X-linked severe combined immunodeficiency. Ann Dermatol Venereol 135(8–9):587–590CrossRefPubMed
58.
Omenn GS (1965) Familial reticuloendotheliosis with eosinophilia. N Engl J Med 273:427–432PubMed
59.
Schandene L, Ferster A et al (1993) T helper type 2-like cells and therapeutic effects of interferon-gamma in combined immunodeficiency with hypereosinophilia (Omenn's syndrome). Eur J Immunol 23(1):56–60CrossRefPubMed
60.
Netea MG, Brouwer AE et al (2004) Two patients with cryptococcal meningitis and idiopathic CD4 lymphopenia: defective cytokine production and reversal by recombinant interferon-gamma therapy. Clin Infect Dis 39(9):e83–e87CrossRefPubMed
61.
62.
Altare F, Lammas D et al (1998) Inherited interleukin 12 deficiency in a child with bacille Calmette-Guerin and Salmonella enteritidis disseminated infection. J Clin Invest 102(12):2035–2040CrossRefPubMed
63.
de Jong R, Altare F et al (1998) Severe mycobacterial and Salmonella infections in interleukin-12 receptor-deficient patients. Science 280(5368):1435–1438CrossRefPubMed
64.
Remiszewski P, Roszkowska-Sliz B et al (2006) Disseminated Mycobacterium avium infection in a 20-year-old female with partial recessive IFNgammaR1 deficiency. Respiration 73(3):375–378CrossRefPubMed
65.
Chatila T, Castigli E et al (1990) Primary combined immunodeficiency resulting from defective transcription of multiple T-cell lymphokine genes. Proc Natl Acad Sci U S A 87(24):10033–10037CrossRefPubMed
66.
Castigli E, Pahwa R et al (1993) Molecular basis of a multiple lymphokine deficiency in a patient with severe combined immunodeficiency. Proc Natl Acad Sci U S A 90(10):4728–4732CrossRefPubMed
67.
Pahwa R, Chatila T et al (1989) Recombinant interleukin 2 therapy in severe combined immunodeficiency disease. Proc Natl Acad Sci U S A 86(13):5069–5073CrossRefPubMed
68.
Aldrich RA, Steinberg AG et al (1954) Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea. Pediatrics 13(2):133–139PubMed
69.
Jin Y, Mazza C et al (2004) Mutations of the Wiskott–Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood 104(13):4010–4019CrossRefPubMed
70.
Azuma H, Oshima M et al (2000) Impaired interleukin-2 production in T-cells from a patient with Wiskott–Aldrich syndrome: basis of clinical effect of interleukin-2 replacement therapy. Eur J Pediatr 159(8):633–634CrossRefPubMed
71.
Azuma H, Sakata H et al (1993) Effect of interleukin 2 on intractable herpes virus infection and chronic eczematoid dermatitis in a patient with Wiskott–Aldrich syndrome. Eur J Pediatr 152(12):998–1000CrossRefPubMed
72.
Hanson EP, Monaco-Shawver L et al (2008) Hypomorphic nuclear factor-kappaB essential modulator mutation database and reconstitution system identifies phenotypic and immunologic diversity. J Allergy Clin Immunol 122(6):1169–1177, e1116CrossRefPubMed
73.
Orange JS, Brodeur SR et al (2002) Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest 109(11):1501–1509PubMed
74.
Cunningham-Rundles C, Bodian C (1999) Common variable immunodeficiency: clinical and immunological features of 248 patients. Clin Immunol 92(1):34–48CrossRefPubMed
75.
Cunningham-Rundles C, Bodian C et al (2001) Long-term low-dose IL-2 enhances immune function in common variable immunodeficiency. Clin Immunol 100(2):181–190CrossRefPubMed
76.
Rump JA, Jahreis A et al (1997) A double-blind, placebo-controlled, crossover therapy study with natural human IL-2 (nhuIL-2) in combination with regular intravenous gammaglobulin (IVIG) infusions in 10 patients with common variable immunodeficiency (CVID). Clin Exp Immunol 110(2):167–173PubMed
77.
Cunningham-Rundles C, Mayer L et al (1992) Restoration of immunoglobulin secretion in vitro in common variable immunodeficiency by in vivo treatment with polyethylene glycol-conjugated human recombinant interleukin-2. Clin Immunol Immunopathol 64(1):46–56CrossRefPubMed
78.
Ten RM, Anderson PM et al (2002) Interleukin-2 liposomes for primary immune deficiency using the aerosol route. Int Immunopharmacol 2(2–3):333–344CrossRefPubMed
79.
Flomenberg N, Welte K et al (1983) Immunologic effects of interleukin 2 in primary immunodeficiency diseases. J Immunol 130(6):2644–2650PubMed
80.
Herzmann C, Cuthbertson Z et al (2008) Long-term clinical and surrogate marker effects of subcutaneous intermittent interleukin-2 without antiretroviral therapy in HIV-infected patients. J Antimicrob Chemother 62(3):583–586CrossRefPubMed
81.
Taylor AM, Harnden DG et al (1975) Ataxia telangiectasia: a human mutation with abnormal radiation sensitivity. Nature 258(5534):427–429CrossRefPubMed
82.
Doi S, Saiki O et al (1989) Administration of recombinant IL-2 augments the level of serum IgM in an IL-2 deficient patient. Eur J Pediatr 148(7):630–633CrossRefPubMed
83.
Sullivan KE (2008) Chromosome 22q11.2 deletion syndrome: DiGeorge syndrome/velocardiofacial Syndrome. Immunol Allergy Clin North Am 28(2):353–366CrossRefPubMed
84.
Markert ML, Hummell DS et al (1998) Complete DiGeorge syndrome: persistence of profound immunodeficiency. J Pediatr 132(1):15–21CrossRefPubMed
85.
Cunningham-Rundles C, Murray HW et al (1999) Treatment of idiopathic CD4 T lymphocytopenia with IL-2. Clin Exp Immunol 116(2):322–325CrossRefPubMed
86.
Yilmaz-Demirdag Y, Wilson B et al (2008) Interleukin-2 treatment for persistent cryptococcal meningitis in a child with idiopathic CD4(+) T lymphocytopenia. Allergy Asthma Proc 29(4):421–424CrossRefPubMed
87.
Gaspari AA, Zalka AD et al (1997) Successful treatment of a generalized human papillomavirus infection with granulocyte-macrophage colony-stimulating factor and interferon gamma immunotherapy in a patient with a primary immunodeficiency and cyclic neutropenia. Arch Dermatol 133(4):491–496CrossRefPubMed
88.
Narula S, LaRosa DF et al (2007) Progressive multifocal leukoencephalopathy in a patient with common variable immunodeficiency and abnormal CD8+ T-cell subset distribution. Ann Allergy Asthma Immunol 98(5):483–489PubMedCrossRef
Metadata
Title
Use of Cytokine Therapy in Primary Immunodeficiency
Authors
Sumita Roy-Ghanta
Jordan S. Orange
Publication date
01-02-2010
Publisher
Humana Press Inc
Published in
Clinical Reviews in Allergy & Immunology / Issue 1/2010
Print ISSN: 1080-0549
Electronic ISSN: 1559-0267
DOI
https://doi.org/10.1007/s12016-009-8131-4

Other articles of this Issue 1/2010

Clinical Reviews in Allergy & Immunology 1/2010 Go to the issue

OriginalPaper

Crohn’s Disease: an Immune Deficiency State

OriginalPaper

Genetic Insights into Congenital Neutropenia

OriginalPaper

Defects in the Leukocyte Adhesion Cascade

OriginalPaper

The Role of Toll-Like Receptor Signaling in Human Immunodeficiencies

OriginalPaper

Hematopoetic Stem Cell Transplantation in Neutrophil Disorders: Severe Congenital Neutropenia, Leukocyte Adhesion Deficiency and Chronic Granulomatous Disease

OriginalPaper

Chronic Granulomatous Disease
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

Read more

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Pediatric Cardiology Video

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

Cardiopulmonary Comorbidity Video

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Valvular Heart Disease Video

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Heart Failure Video

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.

Watch now

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits