Along with its widely recognised role in cancer, lung diseases and cardiovascular diseases, smoking also has wide-ranging and severe impacts on the immune system. It increases inflammation levels, increases the risk of allergic conditions, increases the incidence of autoimmune diseases, decreases immune responses to infectious diseases and increases infection rates.1 The 2014 US Surgeon General’s report concluded that components of cigarette smoke have both immune activating and immune-suppressive effects.2
This section describes the effects of smoking on chronic inflammation and autoimmune diseases. See Section 3.9 for a description of how cigarette smoke increases the susceptibility to infection of smokers.
Inflammation
Inflammation is a response of the immune system to a range of stimuli. These include infections, injuries, damage from heat or chemical burns, poisoning, as well as conditions such as autoimmune diseases and atherosclerosis (hardening of the arteries). Inflammation involves an influx of immune cells, usually white blood cells, into an area of damage or infection. Inflammation is a process used to fight infections, clear damage, and heal wounds. Counterintuitively, inflammation itself can cause damage, particularly if it continues unresolved for a long period of time.2,3
Acute (short-term) inflammation usually last for a few days. Causes include injuries and bacterial infections. Chronic inflammation refers to long-term conditions. Often chronic inflammation occurs as an aberration of the immune system, where it inadvertently attacks the body rather than responding to a pathogen or clearing damage. This section discusses chronic inflammatory conditions affected by smoking, particularly autoimmune diseases.
Cigarette smoke has pro-inflammatory effects that trigger an inflammatory response. This occurs both in the lungs and in the rest of the body. The chemicals present in cigarette smoke interact with various different cell types of the immune system, increasing the numbers of cells that accumulate at site of inflammation and changing the levels of cytokines (signalling molecules released by immune cells)1 and other biological molecules that regulate inflammation.2
Autoimmune diseases
Autoimmune diseases are a range of at least 80 conditions in which the immune system attacks the body. In these diseases, an immune response is raised to a healthy part of the person’s own body, rather than to an invading pathogen or an injury. Chronic inflammation is a common symptom for people with autoimmune diseases and leads to damage that causes problems specific to each separate disease. Autoimmune diseases are usually long-term conditions without a cure, however treatments that reduce inflammation can improve quality of life for people suffering many of these conditions. The exact causes—that is, the reasons why the immune system attacks the body—are usually unknown. Many autoimmune diseases involve production of antibodies that recognise parts of the body rather than pathogens.4 These auto-antibodies direct immune responses to damage normal tissues. Another feature of some autoimmune diseases are white blood cells called T-cells that recognise and attack normal cells rather than virally infected cells, their standard target.2
3.17.1 Rheumatoid arthritis
Rheumatoid arthritis is an autoimmune disease characterised by joint inflammation, pain, swelling, stiffness and loss of function. Rheumatoid arthritis most commonly affects synovial joints, such as those in the hands, arms, knees and feet. Many people with rheumatoid arthritis suffer debilitating fatigue which makes it difficult to participate fully in life.5,6About 456,000 Australians (1.9% of the total population) have rheumatoid arthritis, based on self-reported data from 2017–18, with the prevalence being higher for women (2.3%) than for men (1.5%).6
Several auto-antibodies are involved in the pathophysiology of rheumatoid arthritis, of which rheumatoid factor (RF) and anti-citrullinated protein antibodies (ACPA) are the most common.7 The presence of RF and/or ACPA antibodies in a joint activates and attracts immune cells. Pro-inflammatory signaling molecules are subsequently released by these cells, which can amplify the immune response and contribute to chronic inflammation of and damage to the joint.7,8
The 2014 US Surgeon General’s report concluded that cigarette smoking is a cause of rheumatoid arthritis.2 The risk of developing rheumatoid arthritis is between 1.4 and 4 times higher for people who smoke compared to those who have never smoked, with evidence suggesting that there is a dose-response relationship between smoking and the risk of disease development.2 Rheumatoid arthritis patients who smoke have been shown to have higher levels of RF antibodies compared to patients who have never smoked.9-11 The interaction between smoking and genetic factors may explain this association. However, further research is warranted to clarify the exact mechanism.12 Observational studies have found that current smoking is associated with greater disease activity and lower health-related quality of life among rheumatoid arthritis patients.13,14
Immunosuppressant and anti-inflammatory drugs are effective treatment options for rheumatoid arthritis.15 However, smoking reduces the efficacy of and response to many drug treatments.2,16,17 One example is methotrexate, a common immunosuppressant used in the treatment of rheumatoid arthritis. A 2023 systematic review and meta-analysis found that patients with rheumatoid arthritis who smoked were 2.69 times more likely to have no benefit from methotrexate compared to patients who did not smoke.17 Similarly, tumour necrosis factor alpha (TNFα) inhibitors reduce inflammation associated with rheumatoid arthritis by blocking the effects of TNFα, a pro-inflammatory signalling molecule.18 An observational study found that rheumatoid arthritis patients who smoked were less likely to benefit from TNFα inhibitors compared to those who did not smoke.16
A 2022 systematic review and meta-analysis assessing smoking cessation interventions used among rheumatoid arthritis patients found that cessation rates ranged between 4% and 43% depending on the intervention, duration of follow-up period, and quality of the study.19 Further research is necessary to determine whether smoking cessation reduces the risk, severity, and progression of the disease.19,20 For more information on cessation interventions for people with health conditions see Section 7.12.
3.17.2 Anal abscess and fistula
Anal abscess is an inflammatory disease of the skin around the anus. Inflammation causes sores, or ulcers, to form on the inside wall of the bowel. Those ulcers can extend through the entire thickness of the bowel wall, creating a tunnel (or ‘fistula’) to drain the pus from the infected area through an abscess on the skin on or near the anus. The fistula remains even if the abscess is successfully treated with antibiotics and this is prone to constant inflammation and re-infection.21 A small case–control study of 74 patients with anal abscess/fistula found that smoking within the previous year doubled the risk of this condition.22 Further evidence resulted from a case–control study in 2018. This study of a Chinese population found people with an anal abscess had a 12.3-fold higher odds of a history of smoking compared to people without the condition.23
3.17.3 Graves’ disease
Graves’ disease is an autoimmune disease that affects the thyroid gland, usually leading to an enlargement of the gland and increased production of thyroid hormones. Some symptoms, such as insomnia, weight-loss, and sweating, result from the changes in thyroid hormones, whereas symptoms such as swelling and complications affecting the eyes are a result of autoimmune inflammation.24
Genetic factors account for most of the risk for Graves’s disease, with environmental risk factors accounting for approximately 21% of the risk.25 Smoking is a risk factor for Graves’ disease, but there is currently insufficient evidence to conclude that smoking is a cause. A case–control study from 1993 found that smokers had a 1.9-fold higher odds of developing Grave’s disease than non-smokers.26 In addition, a 2023 population-based study found that smoking exacerbated the risk of developing Grave’s disease among those who already had a family history of the disease.27
Smoking is also a risk factor for a rare complication of Grave’s disease called Graves’ ophthalmopathy.28 For more details, see Section 3.10.4.
3.17.4 Psoriasis (see Skin 3.14.4)
3.17.5 Systemic lupus erythematosus (see Skin 3.14.5)
3.17.6 Diabetes (see Smoking and Diabetes in Section 3.16)
3.17.7 Multiple Sclerosis
Multiple sclerosis is an autoimmune disease of the central nervous system (the brain, spinal cord, and optic nerves).29 This disease occurs when the immune system attacks the myelin sheath, a protective covering surrounding nerve cells. This results in the development of lesions and demyelination, which subsequently disrupt nerve cell signaling.29 The clinical presentation of multiple sclerosis depends on the location and severity of lesions and demyelination. Disease progression also varies, with some patients experiencing relapsing and/or progressive symptoms.30 For information about other neurological diseases, see section 3.18.2.
Smoking is considered to be a risk factor for multiple sclerosis.2,31,32 However, there is evolving research that suggests smoking may have a causative role in the development of this disease. A 2017 systematic review and meta-analysis exploring the association between smoking and multiple sclerosis pooled data from 36 studies, of which 28 case-control, four cross-sectional, and four cohort studies were included. The meta-analysis demonstrated that people who smoke had around a 50% higher risk of developing multiple sclerosis compared to people who did not smoke.33 The authors utilised the “Bradford Hill” criteria to assess causality, and concluded that there was strong evidence of a causal relationship between smoking and the risk of developing multiple sclerosis, and moderate evidence of a causal role of smoking in disease progression.33
Numerous studies have found that multiple sclerosis patients who smoke may have a higher risk of greater disease severity and complications, including increased respiratory symptoms,34 greater brain atrophy,35-37 worse cognitive function,36,38 higher disability burden,39,40 and higher frequency of relapse.41 Some of these disease outcomes have been found to be reversible with cessation.31
The biological mechanisms that underpin the association between smoking and multiple sclerosis are unclear, however several potential mechanisms have been suggested. Cigarette smoke contains nitric oxide, which may play a role in the degradation of nerve tissue.40,42,43 Free radicals, cyanates, and carbon monoxide in cigarette smoke may also be toxic to nerve cells.31 People who smoke experience long-term inflammation and changes to the regulation of inflammatory cells that may play a role in causing autoimmune diseases such as multiple sclerosis.40 People who smoke also have a higher risk of cardiovascular diseases which also increases their risk of multiple sclerosis progression.40,44
3.17.8 Primary biliary cirrhosis
Primary biliary cirrhosis is a rare autoimmune disease of the liver. Numerous studies have shown that smokers are more likely to develop this disease compared to non-smokers.45-47 A systematic review and meta-analysis from 2019 found that the odds of primary biliary cirrhosis for ever smokers was significantly higher than non-smokers (odds ratio of 1.31). Smoking was also associated with an increased risk of more severe disease46,48 and mortality from this condition.49 For more details, see Section 3.12.3.
3.17.9 Inflammatory Bowel Disease (see Section 3.12.2)
3.17.10 Other autoimmune diseases
There is some evidence of an effect of smoking on other chronic inflammatory and autoimmune diseases. However, the evidence is insufficient for making specific conclusions about smoking being an independent risk factor or a cause.
Smoking may be a risk factor for a rare disease called chronic periaortitis (inflammation surrounding the aorta).50 Smoking may also be a risk factor for microscopic colitis, a common cause of chronic, non-bloody diarrhoea.51
Relevant news and research
For recent news items and research on this topic, click here. (Last updated March 2024)
References
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