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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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Related in: MedlinePlus

Peripheral and central mechanisms of opioid-induced immune suppression. Different opioids can have direct effects on immune cells, which express appropriate receptors such as mu-opioid receptors (MORs) and TLR4. They can also have immunosuppressive effects on specific immune cells via central mechanisms. Acute opioid administration enhances activity in the periaqueductal gray (PAG) matter, which activates the sympathetic nervous system (SNS). The SNS innervates lymphoid organs, such as the spleen, and this activation induces the release of biologic amines, which suppress splenic lymphocyte proliferation and natural killer (NK) cell cytotoxicity (Irwin et al, 1988; Fecho et al, 1996). Second, prolonged use of opioids increases hypothalamic pituitary adrenal (HPA) axis activity and glucocorticoid production, which decrease NK cell cytotoxicity (Fecho et al, 1996; Mellon and Bayer, 1998). Morphine can also act via D1 dopamine receptors in the nucleus accumbens shell, increasing the release of neuropeptide Y (NPY) and reducing splenic NK cell cytotoxicity in rodent models (Saurer et al, 2006).
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fig3: Peripheral and central mechanisms of opioid-induced immune suppression. Different opioids can have direct effects on immune cells, which express appropriate receptors such as mu-opioid receptors (MORs) and TLR4. They can also have immunosuppressive effects on specific immune cells via central mechanisms. Acute opioid administration enhances activity in the periaqueductal gray (PAG) matter, which activates the sympathetic nervous system (SNS). The SNS innervates lymphoid organs, such as the spleen, and this activation induces the release of biologic amines, which suppress splenic lymphocyte proliferation and natural killer (NK) cell cytotoxicity (Irwin et al, 1988; Fecho et al, 1996). Second, prolonged use of opioids increases hypothalamic pituitary adrenal (HPA) axis activity and glucocorticoid production, which decrease NK cell cytotoxicity (Fecho et al, 1996; Mellon and Bayer, 1998). Morphine can also act via D1 dopamine receptors in the nucleus accumbens shell, increasing the release of neuropeptide Y (NPY) and reducing splenic NK cell cytotoxicity in rodent models (Saurer et al, 2006).

Mentions: The immunoregulatory effects of morphine and some other opioids can also be elicited by direct effects on immune cells expressing non-opioid receptors such as Toll-like receptor 4 (TLR4) (Wang et al, 2002; Borner et al, 2008, 2009; Keiser et al, 2009; Hutchinson et al, 2010; Franchi et al, 2012). Opioids can also have indirect effects that manifest via centrally produced mediators such as immunosuppressive glucocorticoids that are released as a consequence of hypothalamic pituitary adrenal axis activation, and via effects on the sympathetic nervous system, which innervates lymphoid organs (Figure 3; Wang et al, 2002).


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)

Peripheral and central mechanisms of opioid-induced immune suppression. Different opioids can have direct effects on immune cells, which express appropriate receptors such as mu-opioid receptors (MORs) and TLR4. They can also have immunosuppressive effects on specific immune cells via central mechanisms. Acute opioid administration enhances activity in the periaqueductal gray (PAG) matter, which activates the sympathetic nervous system (SNS). The SNS innervates lymphoid organs, such as the spleen, and this activation induces the release of biologic amines, which suppress splenic lymphocyte proliferation and natural killer (NK) cell cytotoxicity (Irwin et al, 1988; Fecho et al, 1996). Second, prolonged use of opioids increases hypothalamic pituitary adrenal (HPA) axis activity and glucocorticoid production, which decrease NK cell cytotoxicity (Fecho et al, 1996; Mellon and Bayer, 1998). Morphine can also act via D1 dopamine receptors in the nucleus accumbens shell, increasing the release of neuropeptide Y (NPY) and reducing splenic NK cell cytotoxicity in rodent models (Saurer et al, 2006).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Peripheral and central mechanisms of opioid-induced immune suppression. Different opioids can have direct effects on immune cells, which express appropriate receptors such as mu-opioid receptors (MORs) and TLR4. They can also have immunosuppressive effects on specific immune cells via central mechanisms. Acute opioid administration enhances activity in the periaqueductal gray (PAG) matter, which activates the sympathetic nervous system (SNS). The SNS innervates lymphoid organs, such as the spleen, and this activation induces the release of biologic amines, which suppress splenic lymphocyte proliferation and natural killer (NK) cell cytotoxicity (Irwin et al, 1988; Fecho et al, 1996). Second, prolonged use of opioids increases hypothalamic pituitary adrenal (HPA) axis activity and glucocorticoid production, which decrease NK cell cytotoxicity (Fecho et al, 1996; Mellon and Bayer, 1998). Morphine can also act via D1 dopamine receptors in the nucleus accumbens shell, increasing the release of neuropeptide Y (NPY) and reducing splenic NK cell cytotoxicity in rodent models (Saurer et al, 2006).
Mentions: The immunoregulatory effects of morphine and some other opioids can also be elicited by direct effects on immune cells expressing non-opioid receptors such as Toll-like receptor 4 (TLR4) (Wang et al, 2002; Borner et al, 2008, 2009; Keiser et al, 2009; Hutchinson et al, 2010; Franchi et al, 2012). Opioids can also have indirect effects that manifest via centrally produced mediators such as immunosuppressive glucocorticoids that are released as a consequence of hypothalamic pituitary adrenal axis activation, and via effects on the sympathetic nervous system, which innervates lymphoid organs (Figure 3; Wang et al, 2002).

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