FRCA Notes

Effects of Opioids on the Immune System

Resources

  • Perioperative immunosuppression/impaired immunity is undesirable as it is implicated in:
    • Surgical complications including wound infection
    • Spread of cancer (controversial)

  • Pain itself impairs immune function by affecting HPA axis function and suppressing NK cells
  • These deleterious effects can be minimised by adequately reducing nociception and the stress response
  • However, opioids themselves have been demonstrated to have negative effects on the immune system

  • Animal knockout models suggest the MOP receptor mediates the immune effects of opioids
Immunosuppressive effects of opioids
Impaired chemotactic and phagocytic function of neutrophils, monocytes, macrophages
Impair the response, and promote the apoptosis, of B- and T-lymphocytes
Impair mitogen-induced NK cell function, antibody function and lymphocyte proliferation
Central actions impairing corticosteroid production and affecting noradrenaline levels
Central actions on glial cells, which express opioid receptors
Suppression of both cell-mediated and humoral immunity in mouse and human studies
Interaction with the toll-like receptor 4 (TLR4), which is involved in immune signalling
Immune cells can produce and release a range of opioid peptides which act on the endogenous opioid system; the so-called neuro-immune axis
N/OFQ release occurs from human polymorphonuclear cells and lymphocytes in in vitro models

Differential effects

  • Animal models of acute and chronic opioid administration suggest that there are differential effects of opioids on the immune system
    • Fentanyl appears to be maximally immunosuppressive
    • Morphine demonstrates some immunosuppression
    • Buprenorphine, oxycodone and hydromorphone appear to lack immunosuppressive effect
    • Tramadol has putative immuno-protective effects

  • The clinical relevance of these findings is unknown and it is not suggested that practice is changed on this basis

  • See the page on malignancy for further information
  • Opioids may influence cancer by
    • Immune system depression via unclear mechanisms
    • Modulating angiogenesis
    • Directly affecting cancer cell biology

  • The oncological effects of opioids depend on the cancer (sub-)type
    • Opioids may be oncogenic in some cancer types e.g. non-small cell lung cancer, clear cell renal carcinoma
    • Conversely, they may be anti-tumour in triple negative breast cancer and colonic adenocarcinoma

  • Patient-specific tumour genomics and transcriptomics may further determine effect of opioids on outcome
  • Overall there is insufficient evidence to associate opioid use with cancer promotion or spread

  • Evidence of cardiovascular dysfunction relating to the immune response in sepsis suggests cross-talk between these two systems; an immune-vascular axis
  • Critically ill patients demonstrate increased plasma levels of N/OFQ
  • The theory is that these higher levels result from immune cell release of N/OFQ, which in turn activates NOP receptor upregulation on vascular endothelium and consequent cardiovascular effects
  • In animal models, higher N/OFQ levels are linked to increased mortality and is associated with hypotension, vasodilation and macromolecular leaks
  • N/OFQ antagonism might be a beneficial adjunct for management of sepsis-induced cardiovascular instability