What are the effects of THC on NK cell ratios, TNF-alpha:IL-10 ratio, and IFN-gamma:IL-10 ratio in CD3+CD4+ T cells, especially in patients with compromised immune systems?

Medical Advisory BoardAll articles are reviewed for accuracy by our Medical Advisory Board
Educational purpose only • Exercise caution as content is pending human review
Article Review Status
Submitted
Under Review
Approved

Last updated: February 1, 2026 • View editorial policy

Personalize

Help us tailor your experience

Which best describes you? Your choice helps us use language that's most understandable for you.

THC Effects on NK Cells and Cytokine Ratios in Immunocompromised Patients

Direct Answer

THC significantly impairs NK cell function and shifts cytokine ratios toward immunosuppression by decreasing TNF-alpha and IFN-gamma while variably affecting IL-10, creating an unfavorable immune profile that is particularly dangerous in immunocompromised patients. 1, 2

Effects on Natural Killer (NK) Cells

THC directly suppresses NK cell cytotoxic activity and function, which is critical for immune surveillance against tumors and infections. 1

  • The 2024 ASCO guidelines explicitly state that cannabinoids modulate the function of natural killer cells, along with dendritic cells and other immune components. 1
  • In vitro studies demonstrate that THC suppresses NK cell activity in a dose-dependent manner. 3
  • This NK cell suppression has real clinical consequences: patients with cancer receiving immunotherapy who use cannabis show reduced response rates, decreased time to tumor progression, and decreased overall survival. 2

Effects on TNF-alpha:IL-10 Ratio in CD3+CD4+ T Cells

THC decreases the TNF-alpha:IL-10 ratio by suppressing TNF-alpha production while having variable effects on IL-10, creating an anti-inflammatory shift that impairs protective immunity. 4, 5, 6

TNF-alpha Suppression:

  • THC at concentrations of 5-10 μg/ml significantly decreases TNF-alpha production by macrophages in a dose-dependent manner. 4
  • Even pretreatment with lower THC concentrations (0.1-1.0 μg/ml) for 3 hours decreases TNF-alpha production capacity. 4
  • THC inhibits phorbol ester-stimulated TNF-alpha production by NK cells. 5
  • Macrophages treated with THC show increased TNF-alpha in some contexts but overall suppression in stimulated cultures relevant to immune responses. 6

IL-10 Effects:

  • THC strongly inhibits IL-10 production by T cells (HUT-78 T-cell line). 5
  • However, THC increases IL-10 detection in splenocyte cultures stimulated with pokeweed mitogen, suggesting context-dependent effects. 6
  • The net effect is immunosuppressive because the TNF-alpha suppression is more consistent and pronounced than IL-10 changes. 4, 5

Effects on IFN-gamma:IL-10 Ratio in CD3+CD4+ T Cells

THC dramatically decreases the IFN-gamma:IL-10 ratio by suppressing IFN-gamma production while variably affecting IL-10, shifting the immune response from Th1 (cell-mediated) to Th2 (humoral) patterns. 5, 6

IFN-gamma Suppression:

  • THC decreases IFN-gamma production in splenocyte cultures, a hallmark of Th1 response suppression. 6
  • THC inhibits phorbol ester-stimulated IFN-gamma production by NK cells. 5
  • The suppression occurs through decreased production of upstream cytokines IL-12 and IL-15, which normally induce IFN-gamma from T cells and NK cells. 6

Mechanistic Basis:

  • THC suppresses IL-12 and IL-15 production by macrophages, which are critical for inducing Th1 responses and IFN-gamma production. 6
  • Macrophage depletion studies confirm that macrophages are central to THC's effects on the cytokine network. 6
  • THC fundamentally shifts the immune response from Th1 (protective against intracellular pathogens and tumors) to Th2 (humoral immunity), which is detrimental in immunocompromised states. 6

Critical Clinical Implications for Immunocompromised Patients

Cannabis use should be strongly advised against in immunocompromised patients, particularly those receiving cancer immunotherapy. 1, 2

Specific Risks:

  • THC directly reduces the therapeutic effect of PD-1 blockade by suppressing T-cell antitumor immunity through inhibition of JAK/STAT signaling via cannabinoid receptor type 2. 1
  • Prolonged cannabis consumption interferes with immunotherapy and hinders humoral immunity. 1
  • The immunosuppressive effects include: suppressed T-cell proliferation, activation, and cytotoxic activity; altered cytokine and chemokine production; impaired dendritic and NK cell function; and rapid expansion of immunosuppressive myeloid-derived suppressor cells. 1, 2

Evidence from Clinical Outcomes:

  • Cannabis consumption correlates with reduced response rates to nivolumab in cancer patients. 1
  • Prospective studies show significant decreases in time to tumor progression and overall survival in patients using cannabis during immunotherapy. 1
  • Increased susceptibility to opportunistic infections (e.g., Legionella pneumophila) has been demonstrated in animal models. 3

Additional Immunological Concerns

  • Marijuana smokers show impaired immunological functions, including deficient blood leukocyte blastogenesis to mitogens. 3
  • THC suppresses antibody formation and causes deficient cytokine production in experimental animals. 3
  • Fungal spores in marijuana pose the greatest hazard to immunocompromised patients, though they can be sterilized by several methods. 7

References

1
Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

2
Guideline

Cannabis Use and Immune System Modulation

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

3
Research

Marijuana, receptors and immunomodulation.

Advances in experimental medicine and biology, 1995

6
Research

The role of macrophages in THC-induced alteration of the cytokine network.

Advances in experimental medicine and biology, 1998

7
Research

Medical marijuana and its use by the immunocompromised.

Alternative therapies in health and medicine, 1997

Related Questions

What are alternative anticoagulants to apixaban (Apixaban is a brand name for the generic medication Eliquis, which is a Factor Xa inhibitor) for a patient with suspected Deep Vein Thrombosis (DVT) and high risk of Pulmonary Embolism (PE) who also presents with leukocytosis (elevated white blood cell count)?
How to manage hyponatremia (low sodium levels) in patients with chronic kidney disease (CKD)?
What to do with a patient with suspected Deep Vein Thrombosis (DVT) and high risk of Pulmonary Embolism (PE) who is also presenting with leukocytosis and has an increased Prothrombin Time/International Normalized Ratio (PT/INR)?
What treatment options are available for a female patient of reproductive age with endometriosis who is not immunocompromised?
For a patient with suspected DVT and high risk of PE, presenting with leukocytosis and an elevated PT/INR, how many days should LMWH be initiated before starting Apixaban?
What is the anatomy and function of the basal ganglia in the brain?

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

Have a follow-up question?

Our Medical A.I. is used by practicing medical doctors at top research institutions around the world. Ask any follow up question and get world-class guideline-backed answers instantly.

Ask Question