Cytokine levels in platelet concentrates: quantitation by bioassays and immunoassays

Abstract

Some adverse reactions to the transfusion of platelet concentrates (PCs) cannot be attributed to antibodies against blood cells or to subclinical microbial agents. It has been suggested that leucocyte-derived inflammatory cytokines such as interleukin (IL)-1, IL-6 and tumour necrosis factor (TNF) may contribute to a larger number of unexplained non-antibody-mediated adverse reactions. Three types of PCs, containing different levels of leucocytes, are currently produced. Filtration is used on demand to further reduce leucocyte contamination of these components. we have monitored the plasma of PCs prepared by the platelet-rich plasma method (PRP), the buffy-coat method or by apheresis for IL-6, IL-1, transforming growth factor-beta (TGF-beta), TNF and interferon gamma (IFN gamma). Biologically active IL-6 increased in stored PRP-PCs from a mean of 140 pg/ml on day 1 to 2395 pg/ml on day 5/6. Elevated levels of IL-8, as detected by immunoassay, were evident in PRP-PCs during routine storage under blood bank conditions. Small amounts of immunoreactive IL-1 with only minimal biological activity were present in some PRP-PCs by day 5/6. No significant increase in the levels of IL-8, IL-6 or IL-1 were seen in buffy-coat PCs during storage for 5/6 d. For apheresis PCs, an increase in IL-8 content, but not in IL-6 over 6 d was observed. In all three types of PCs, elevated amounts of both bioactive and immunoreactive TGF beta were present, but there was no evidence of any biologically active or immunoreactive TNF alpha. Pre-storage filtration of PRP-PCs for depletion of leucocytes prevented the increase in IL-8 and IL-6 levels of these PCs. Our results show that leucocyte reduction by buffy-coat method reduces cytokine levels to a comparable level to filtered or apheresis PCs, containing low levels of leucocytes, but use of these PCs in minimizing the severity and incidence of reactions in recipients will require clinical evaluation. This is the first comprehensive and comparative study which, on the basis of biological activity of cytokines, directly indicates that the mode of platelet production grossly influences the levels of cytokines.

Current Understanding of Allergic Transfusion Reactions: Incidence, Pathogenesis, Laboratory Tests, Prevention and Treatment

“…Stored PLT concentrate supernatants (PC-SNs) accumulate striking levels of BRMs during storage, including vascular endothelial growth factor, soluble CD40 ligand, histamine, transforming growth factor-b1 and RANTES (Wadhwa et al, 1996;Edvardsen et al, 1998;Phipps et al, 2001;Wakamoto et al, 2003;Garraud et al, 2012). There is reason to believe that these molecules are infused at what may be clinically significant doses and possibly alter a recipient's immune functions.…”

Platelets should be at the Frontline: HIV Researchers and Care Providers Needs a lot of Sticky Notes

“…Descriptions go from how platelets rapidly deploy host-defense peptides, to enhancing cell recruitment in the context of infection control. The first study of this kind described the interaction of PLTs with Streptococcus; yet thereafter, researchers have demonstrated that the open canalicular system of platelets contributes to the engulfment (and/or "filtration") of several bacterium, viruses, and parasites [10][11]. Notably, prior studies detected higher percentages of dengue viral RNA in PLTS than in plasma and a high positive rate (43%) of dengue viral RNA in PLTs, indicating that PLTs sustain viral replication [4].…”

“…Notably, CD40 and platelets have been recently linked to intestinal pathological processes, which can elicit microbial transmigration and thus create a vicious cycle by inducing further inflammation [9][10][11]18]. CD40-CD40L interaction also suppresses interferon α production, which is a well-known player in the antiviral response.…”

“…Interrogation of an arrayed cDNA library proved that platelets contain many cytokine messenger RNAs [9][10][11]. Second, platelets have been shown to express chemokine receptors, such as MIP-1α, PDGF, and RANTES (the Macrophage Inflammatory Protein, the Platelet derived growth factor and the Regulated on Activation, Normal T Cell Expressed and Secreted) that trigger the chemotaxis of other cells to the sites of inflammation [9][10][11]18].…”

“…The list of cytokines de novo produced by platelets now includes: TGF-β1, IL-4, IL-8, IL-13, IL-17, IFNα and TNFα [9][10][11].…”