Immunomodulatory effects of surgical trauma and blood transfusion.
Major surgical trauma and allogeneic transfusions cause
immunomodulation, a systemic condition characterised by a reduction in natural
killer (NK) cell function, macrophage migration, antigen presentation, proinflammatory
cytokine synthesis and lymphocyte blastogenesis. Clinically there is
increased tumour recurrence, increased post-operative infections, delayed
wound healing, prolonged hospital stay and increased mortality.
Immunomodulation affects innate immunity as reflected in NK cell function.
Hence a method was developed to measure the NK cell precursor frequency
(NKpf) in samples of peripheral blood mononuclear cells (PBMC). The technique
was based on the principle of limiting dilution analysis and was performed in the
presence of recombinant interleukin two (rIL-2) and rIL-15. After five day's culture
lysis of the K562 cell-line was measured and NKpf calculated. NKpf was
measured before and after joint replacement surgery in 120 orthopaedic patients
assigned to five groups according to the type of transfused blood they received,
namely: allogeneic non-Ieukodepleted; allogeneic leukodepleted; autologous
unwashed blood salvaged post-operatively from the operation site (autologous
salvaged), and autologous pre-deposit. The fifth group was non-transfused.
Interferon-gamma (IFNy), IL-10 and IL-4 synthesis were measured in
supernatants of similar cultures and flow-cytometry was used to measure
percentage of the CD3 negative cells that were CD56 positive in the five-day
The results showed all groups had significantly decreased post-operative
NKpf (p<0.05), and non significant decreased post-operative IFNy and IL-10
synthesis (p>0.05) except the autologous salvaged group. By contrast, the latter
showed a significant rise in post-operative NKpf values (p<0.05) and a non
significant increase in IFNy and IL-10 synthesis (p>0.05). IL-4 and
immunophenotyping studies were inconclusive. The proportion developing postoperative
infections in those who received allogeneic blood (non-Ieukodepleted and leukodepleted) was 15% compared to 80/0 in those who received autologous
blood (pre-deposit and salvaged) and 12% in the non-transfused group.
It was concluded that, major surgical trauma could be associated with
impairment of NK cell potential, decreased IFNy and IL-10 synthesis and that
allogeneic transfusions add to these effects even after leukodepletion. These
effects could lead to an increased risk of post-operative infections. By contrast
autologous salvaged blood reverses these systemic effects perhaps by
transferring locally synthesised cytokines and chemokines from the operation site
to the circulation.