Analysis of cytokine secretion from lymphocytes of patients with hypersensitivity reactions to contaminated heparins.
BACKGROUND
Beginning in 2007, anaphylactoid reactions associated with unfractionated heparin (UFH) occurred and resulted in some fatalities. These reactions were reported to be linked to the complement and contact system activation induced by certain batches of UFH containing the adulterant oversulphated chondroitin sulphate (OSCS).


OBJECTIVE
Drug-specific secretion of selected cytokines from peripheral blood mononuclear cells (PBMC) of patients with hypersensitivity reactions to contaminated heparin was compared with the respective in vitro cytokine pattern of individuals with or without hypersensitivity to heparin, different glycosaminoglycans or other drugs.


METHODS
Study individuals (n = 13) were classified as follows: patients with hypersensitivity reactions to contaminated (OSCS) heparin (n = 3), noncontaminated heparin (n = 1) or other compounds (n = 3) and patients with ongoing heparin therapy without symptoms of intolerance (n = 2). Four healthy individuals served as controls. PBMC were incubated with six different glycosaminoglycan structures. Drug-specific intracellular interleukin (IL)-5, interferon (IFN)-γ and IL-10 production was investigated by flow cytometry, while secretion of IL-5, IL-2 and IFN-γ was analysed by enzyme-linked immunosorbent assay.


RESULTS
PBMC from individuals with hypersensitivity reactions to contaminated heparin secreted considerable amounts of IL-2 in vitro. There was a suggestion that ongoing heparin therapy and the Li-heparin in the vials may have an impact on the lymphocyte reactivity of PBMC.


CONCLUSIONS
The in vitro lymphocyte reactivity pattern of PBMC from individuals with hypersensitivity reactions to contaminated heparins was neither typical for an immune-mediated nor for a nonimmune-mediated reaction. Possible effects of heparins in the test system itself may require consideration.
Martin
M
M
Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany. mail@marion-martin.info
Ott
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Merk
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Sachs
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000707:Anaphylaxis / Q000139:chemically induced / Q000276:immunology*; D000925:Anticoagulants / Q000009:adverse effects*; D001491:Basophils / Q000276:immunology; D002809:Chondroitin Sulfates / Q000009:adverse effects; D016207:Cytokines / Q000276:immunology* / Q000378:metabolism; D004340:Drug Contamination; D004342:Drug Hypersensitivity / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006025:Glycosaminoglycans / Q000009:adverse effects; D006493:Heparin / Q000009:adverse effects* / Q000737:chemistry; D006801:Humans; D007371:Interferon-gamma / Q000097:blood; D016753:Interleukin-10 / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D015848:Interleukin-5 / Q000097:blood; D008214:Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D055815:Young Adult
D000925:Anticoagulants; D016207:Cytokines; D006025:Glycosaminoglycans; D007376:Interleukin-2; D015848:Interleukin-5; D016753:Interleukin-10; D007371:Interferon-gamma; D006493:Heparin; D002809:Chondroitin Sulfates