The effects of autologous platelet gel on inflammatory cytokine response in human peripheral blood mononuclear cells

Abstract

The potential therapeutic value and versatility of platelet-derived products has recently stimulated the research and interest in the field of regenerative medicine. Platelet gels (PG), generated by thrombin-activated platelets, represent a new biotechnology for stimulation and acceleration of tissue healing and regeneration. However, despite the diffused and successful use of PG in clinical practice, a more detailed knowledge of the cellular and molecular mechanisms involved is required. In the present study, we show that human peripheral blood mononuclear cells (PBMC) co-cultured with PG, in the presence of the inflammatory activator lipopolysaccharide, secreted higher amounts of pro-inflammatory and pro-angiogenic cytokines, such as interleukin (IL)-1beta, IL-6 and IL-8. In contrast, the release of the anti-angiogenic cytokines interferon-gamma and IL-12 was significantly reduced. In addition the production of the anti-inflammatory cytokine IL-10 was not affected by PG. Finally, hypoxia, a common feature of the healing tissue, potentiated the effects exerted by PG on the release of IL-1beta by PBMC. In conclusion, PG treatment reveals a unique capacity of articulating a pro-inflammatory and pro-angiogenic cytokine profile in human PBMC, which may partially explain the clinical success of PG application in a wide range of diseases.

Activated Platelets Enhance IL-10 Secretion and Reduce TNF-α Secretion by Monocytes

“…This discrepancy might be because of their use of monoclonal anti-CD3/anti-CD28 as a stimulus, which is likely to be much stronger than the more physiological antigenic stimuli used in this study. Using thrombin-generated platelet gels, Naldini et al showed that platelets reduced the release of IFN-g by LPS-stimulated PBMCs (8,38), and supporting their data, we did find a tendency toward platelet-mediated inhibition of TTinduced IFN-g production (Fig. 1B).…”

“…We therefore propose that the inhibitory effect of activated platelets on CD4 + T cell proliferation is directly related to their inhibition of TNF-a, in accordance with findings of Brown et al (37). Unlike other investigators (8,17), we found no effect of platelets on the T cell production of TNF-a, IL-10, IFN-g, IL-2, or IL-4. In particular, platelets influenced neither the frequency of IL-10-secreting CD4 + T cells nor the IL-10 production per individual cell, which disagrees with Gerdes and colleagues (17), who found that platelets enhanced IL-10 production by CD4 + T cells.…”

“…P latelets are well-known as mediators of hemostasis and initiators of wound healing (1)(2)(3). Recent studies suggest that platelets also play a role in modulating adaptive immune responses (4)(5)(6)(7)(8). Upon activation, platelets are capable of secreting a range of immunomodulatory chemokines contained in their a-granula, including platelet factor 4 (PF4), RANTES, and CXCL7 (6,9).…”

Simulated Night Shift Disrupts Circadian Rhythms of Immune Functions in Humans

“…These differences are likely the result of different methods of assessment (e.g., whole blood versus isolated cells; stimulated versus unstimulated cytokine production) and the degree of control of confounding factors (e.g., activity levels, light exposure, food intake). In this study, we used isolated PBMCs to prevent an influence of RBCs and platelets on the levels of cytokines released (45,46,54,55), and we studied cytokine secretion in stimulated cells (using both absolute levels and levels/cell). Under these conditions, the change in the timing of sleep from a day-oriented to a night-oriented schedule did not result in overall changes in the rhythm of immune cell counts or in the amounts of cytokines released with or without stimulation.…”

“…Although we could not eliminate the PBMC-bound platelets, the relative proportion of free platelets was always low (#3.9% of total cell number included in the platelet gate and the PBMC gate) and stable over time. This showed that our thorough washing procedure minimized the presence of platelets in the samples, making it unlikely that cytokine secretion was affected by their presence (45,46). p values , 0.05 were considered significant.…”