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Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review.

Boland JW, McWilliams K, Ahmedzai SH, Pockley AG - Br. J. Cancer (2014)

Bottom Line: Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms.Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made.Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

View Article: PubMed Central - PubMed

Affiliation: Hull York Medical School, University of Hull, Hull HU6 7RX, UK.

ABSTRACT

Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer.

Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed.

Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects.

Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

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Quadrangulation of the effects of opioids on pain, immunity and cancer. Under normal circumstances opioids inhibit pain, which is itself immunosuppressive (Page et al, 2001; Page, 2003). Some opioids also have specific effects on immune function, either suppressive or stimulatory, and the balance of these opioid-mediated effects influences the progression of cancer (in animal models) (Gaspani et al, 2002). The immune system, via microglia and cytokines, influences the pain state (Hutchinson et al, 2008). Activated immune cells can also produce endogenous opioids, as well as morphine (Stein and Lang, 2009; Glattard et al, 2010). Cancer can also cause pain, by nociceptive, neuropathic and inflammatory mechanisms. There is a dynamic interaction of the immune system and cancer with immunoediting and immunosculpting (Reiman et al, 2007). Furthermore, there are non-immune effects of opioids on cancer cells (Gach et al, 2011). All of these factors combine to create the net balance of cancer cell growth or destruction (Page, 2005). The white arrows indicate a beneficial effect on pain, immunity and cancer, and the solid arrows indicate a detrimental effect on immunity and cancer.
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fig2: Quadrangulation of the effects of opioids on pain, immunity and cancer. Under normal circumstances opioids inhibit pain, which is itself immunosuppressive (Page et al, 2001; Page, 2003). Some opioids also have specific effects on immune function, either suppressive or stimulatory, and the balance of these opioid-mediated effects influences the progression of cancer (in animal models) (Gaspani et al, 2002). The immune system, via microglia and cytokines, influences the pain state (Hutchinson et al, 2008). Activated immune cells can also produce endogenous opioids, as well as morphine (Stein and Lang, 2009; Glattard et al, 2010). Cancer can also cause pain, by nociceptive, neuropathic and inflammatory mechanisms. There is a dynamic interaction of the immune system and cancer with immunoediting and immunosculpting (Reiman et al, 2007). Furthermore, there are non-immune effects of opioids on cancer cells (Gach et al, 2011). All of these factors combine to create the net balance of cancer cell growth or destruction (Page, 2005). The white arrows indicate a beneficial effect on pain, immunity and cancer, and the solid arrows indicate a detrimental effect on immunity and cancer.

Mentions: Immune cells express ORL1 when resting and the mu opioid receptor, which is considered to be critical for immune cells to respond directly to most commonly prescribed opioids, following activation (Williams et al, 2007; Borner et al, 2008). Opioid receptor activation triggers multiple downstream signalling events, which include decreasing cyclic adenosine monophosphate (cAMP), increasing nitric oxide and cyclic guanosine monophosphate levels, and the stimulation of phospholipase C, mitogen-activated protein kinase (MAPK) and protein kinase C (Kelly et al, 2008; Stefano et al, 2008). All of these interactions ultimately interfere with immune cell activation pathways, which involve cAMP and MAPK (Borner et al, 2008, 2009). Activated immune cells can produce several opioid peptides (such as β-endorphin) in addition to endogenous morphine that can bind to opioid receptors present on peripheral nerves to induce analgesia (Stein and Lang, 2009; Glattard et al, 2010). The presence of opioid receptors on activated lymphoid cells suggests that endogenous opioids released by such cells could also contribute to an inhibitory feedback loop (Borner et al, 2008). These potential effects are summarised in Figure 2.


Effects of opioids on immunologic parameters that are relevant to anti-tumour immune potential in patients with cancer: a systematic literature review.

Boland JW, McWilliams K, Ahmedzai SH, Pockley AG - Br. J. Cancer (2014)

Quadrangulation of the effects of opioids on pain, immunity and cancer. Under normal circumstances opioids inhibit pain, which is itself immunosuppressive (Page et al, 2001; Page, 2003). Some opioids also have specific effects on immune function, either suppressive or stimulatory, and the balance of these opioid-mediated effects influences the progression of cancer (in animal models) (Gaspani et al, 2002). The immune system, via microglia and cytokines, influences the pain state (Hutchinson et al, 2008). Activated immune cells can also produce endogenous opioids, as well as morphine (Stein and Lang, 2009; Glattard et al, 2010). Cancer can also cause pain, by nociceptive, neuropathic and inflammatory mechanisms. There is a dynamic interaction of the immune system and cancer with immunoediting and immunosculpting (Reiman et al, 2007). Furthermore, there are non-immune effects of opioids on cancer cells (Gach et al, 2011). All of these factors combine to create the net balance of cancer cell growth or destruction (Page, 2005). The white arrows indicate a beneficial effect on pain, immunity and cancer, and the solid arrows indicate a detrimental effect on immunity and cancer.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4150281&req=5

fig2: Quadrangulation of the effects of opioids on pain, immunity and cancer. Under normal circumstances opioids inhibit pain, which is itself immunosuppressive (Page et al, 2001; Page, 2003). Some opioids also have specific effects on immune function, either suppressive or stimulatory, and the balance of these opioid-mediated effects influences the progression of cancer (in animal models) (Gaspani et al, 2002). The immune system, via microglia and cytokines, influences the pain state (Hutchinson et al, 2008). Activated immune cells can also produce endogenous opioids, as well as morphine (Stein and Lang, 2009; Glattard et al, 2010). Cancer can also cause pain, by nociceptive, neuropathic and inflammatory mechanisms. There is a dynamic interaction of the immune system and cancer with immunoediting and immunosculpting (Reiman et al, 2007). Furthermore, there are non-immune effects of opioids on cancer cells (Gach et al, 2011). All of these factors combine to create the net balance of cancer cell growth or destruction (Page, 2005). The white arrows indicate a beneficial effect on pain, immunity and cancer, and the solid arrows indicate a detrimental effect on immunity and cancer.
Mentions: Immune cells express ORL1 when resting and the mu opioid receptor, which is considered to be critical for immune cells to respond directly to most commonly prescribed opioids, following activation (Williams et al, 2007; Borner et al, 2008). Opioid receptor activation triggers multiple downstream signalling events, which include decreasing cyclic adenosine monophosphate (cAMP), increasing nitric oxide and cyclic guanosine monophosphate levels, and the stimulation of phospholipase C, mitogen-activated protein kinase (MAPK) and protein kinase C (Kelly et al, 2008; Stefano et al, 2008). All of these interactions ultimately interfere with immune cell activation pathways, which involve cAMP and MAPK (Borner et al, 2008, 2009). Activated immune cells can produce several opioid peptides (such as β-endorphin) in addition to endogenous morphine that can bind to opioid receptors present on peripheral nerves to induce analgesia (Stein and Lang, 2009; Glattard et al, 2010). The presence of opioid receptors on activated lymphoid cells suggests that endogenous opioids released by such cells could also contribute to an inhibitory feedback loop (Borner et al, 2008). These potential effects are summarised in Figure 2.

Bottom Line: Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms.Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made.Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

View Article: PubMed Central - PubMed

Affiliation: Hull York Medical School, University of Hull, Hull HU6 7RX, UK.

ABSTRACT

Background: The immune system has a central role in controlling cancer, and factors that influence protective antitumour immunity could therefore have a significant impact on the course of malignant disease. Opioids are essential for the management of cancer pain, and preclinical studies indicate that opioids have the potential to influence these tumour immune surveillance mechanisms. The aim of this systematic literature review is to evaluate the clinical effects of opioids on the immune system of patients with cancer.

Methods: A systematic search of Ovid MEDLINE (PubMed) and Embase, Cochrane database and Web of Knowledge for clinical studies, which evaluated the effects of opioids on the immune system in patients with cancer, was performed.

Results: Five human studies, which have assessed the effects of opioids on the immune system in patients with cancer, were identified. Although all of these evaluated the effect of morphine on immunologic end points in patients with cancer, none measured the clinical effects.

Conclusions: Evidence from preclinical, healthy volunteer and surgical models suggests that different opioids variably influence protective anti-tumour immunity; however, actual data derived from cancer populations are inconclusive and definitive recommendations cannot be made. Appropriately designed and powered studies assessing clinical outcomes of opioid use in people with cancer are therefore required to inform oncologists and others involved in cancer care about the rational use of opioids in this patient group.

Show MeSH
Related in: MedlinePlus