Nicotine Is Not a Proinflammatory Component of E-cigarette Vapor

Alteration compared with nonsmoker	Reference
Increase in alveolar inflammatory cells	Niewoehner et al., 1974 (34)
Generation of chemotactic factor C5a	Perricone et al., 1983 (14) Kew et al., 1987 (15)
Inactivation of chemotactic factor inhibitor	Robbins et al., 1990 (16)
Activation of macrophages	Hunninghake and Crystal, 1983 (17)
Activation of epithelial cells	Shoji et al., 1995 (18) Mio et al., 1997 (19)
Four- to five-fold increase in BAL neutrophils	Hunninghake and Crystal, 1983 (17)
Increase in BAL neutrophil elastase levels	Fujita et al., 1990 (20)
Decrease in anti-elastase activity	Carp et al., 1982 (21) Hubbard et al., 1987 (22)
Four- to five-fold increase in BAL macrophages	Shapiro, 1994 (23)
Increase in macrophage metalloelastase	Shapiro, 1994 (23)
Recruitment of inflammatory cells via macrophage generated matrix fragments	Hunninghake et al., 1981 (24) Senior et al., 1980 (25)
Increase in cathepsins B, D, and L	Kominami et al., 1988 (35) Gairola et al., 1989 (27) Chang et al., 1986, 1989 (26, 29) Lesser et al., 1989, 1992 (28, 30)

Table 2.

Subclinical manifestations of pulmonary inflammation in smokers.

Alteration compared with nonsmoker	Reference
Increased respiratory symptoms on SGRSQ; especially morning cough	Jones et al., 1991 (36) Jones et al., 1992 (37) Barr et al., 2000 (38)
Decreased FEF25–75%	McFadden and Linden, 1972 (39) Kwon et al., 2020 (40) Pisi et al., 2021 (41)
Increased clearance of 99m-DTPA	Coates and O'Brodovich, 1986 (42) Stewart et al., 2006 (43)
Abbreviations:
SGRSQ:	St. George's Respiratory Symptom Questionnaire Forced Expiratory Flow (FEF) between 25% and 75% of forced vital capacity ^99m-Technicium-diethylenetriaminepentaacetic acid
FEF_25–75%:
99m-DTPA:

Table 3.

Proinflammatory changes in smokers' systemic circulation.

Alteration compared with nonsmoker	Reference
Increase in C-reactive protein	Madsen et al., 2007 (60)
Increase in glycoprotein acetylation	Kianoush et al., 2017 (61)
Increase in fibrinogen	Tuut and Hense, 2001 (62)
Increase in peripheral white blood cell count	Petitti and Kipp, 1986 (63) Yarnell et al., 1987 (64) Schwartz and Weiss, 1991, 1994 (65–66) Freedman et al., 1996 (67) Sunyer et al., 1996 (68) van Tiel, 2002 (69) Fröhlich et al., 2003 (70) Smith et al., 2003 (71) Lao et al., 2009 (72) Higuchi et al., 2016 (73)

Interaction of pulmonary and systemic inflammation.

Table 4.

T_max and C_max data for nicotine intake from various nicotine sources.

Nicotine source	Absorption site	Absorption speed (peak time (T_max) to maximum blood concentration)	Peak blood level (C_max peak plasma concentration)	References
Cigarettes	Pulmonary vasculature (alveoli to pulmonary veins)	5 min affected by puff intensity and duration. [Nicotine in smoking tobacco is delivered mainly in the form of mixed nicotine salts.]	15 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87) Yingst et al., 2024 (88)
Heat-not-burn device (IQOS)	Oral mucosal vasculature	5 min	13 ng/mL	Yingst et al., 2024 (88) PMI, 2025 (89) Smith et al., 2016 (90)
Small cigars	Oral mucosal vasculature	There were no significant differences in T_max based on cigar type (~60 min)	6 ng/mL	Claus et al., 2018 (91)
Cigarillos	Oral mucosal vasculature	There were no significant differences in T_max based on cigarillo type (~60 min)	8 ng/mL	Claus et al., 2018 (91)
Large cigars	Oral mucosal vasculature	There were no significant differences in T_max based on cigar type (~60 min)	13 ng/mL	Claus et al., 2018 (91)
Moist snuff 18 mg nicotine	Nasal mucosal vasculature	65 min	17 ng/mL	Lunell et al., 2020 (92)
Loose snus 10.8 mg	Oral mucosal vasculature	45 min	8 ng/mL	Renard et al., 2025 (93)
Loose snus 10.8 mg	Oral mucosal vasculature	60 min	11 ng/mL	Digard et al., 2013 (94)
Loose snus 27.1 mg	Oral mucosal vasculature	60 min	18 ng/mL	Digard et al., 2013 (94)
Pouched snus 10.7 mg	Oral mucosal vasculature	60 min	11 ng/mL	Digard et al., 2013 (94)
Pouched snus 14.7 mg	Oral mucosal vasculature	60 min	13 ng/mL	Digard et al., 2013 (94)
Nicotine pouches 6 mg	Oral mucosal vasculature	20 min	3 ng/mL	Mallock-Ohnesorg et al., 2024 (95)
Nicotine pouches 6 mg	Oral mucosal vasculature	30 min	11 ng/mL	Renard et al., 2025 (93)
Nicotine pouches 9 mg	Oral mucosal vasculature	38 min	14 ng/mL	Renard et al., 2025 (93)
Nicotine pouches 11 mg	Oral mucosal vasculature	30 min	17–20 ng/mL	Renard et al., 2025 (93)
Nicotine pouches 11 mg	Oral mucosal vasculature	30 min	17–20 ng/mL	Azzopardi et al., 2026 (96)
Nicotine pouches 20 mg	Oral mucosal vasculature	15 min	7 ng/mL	Mallock-Ohnesorg et al., 2024 (95)
Nicotine pouches 30 mg	Oral mucosal vasculature	15 min	29 ng/mL	Mallock-Ohnesorg et al., 2024 (95)
Nicotine pouches 11 mg	Oral mucosal vasculature	20 min	21 ng/mL	Pickworth et.al. 2014 (97)
Nicotine pouches 11 mg	Oral mucosal vasculature	20 min	21 ng/mL	Azzopardi et al., 2026 (96)
Nicotine pouches 20 mg	Oral mucosal vasculature	20 min	30 ng/mL	Azzopardi et al., 2026 (96)
Tobacco-free nicotine pouches (ZYN) 3 mg	Oral mucosal vasculature	61 min	8 ng/mL	Azzopardi et al., 2026 (96)
Tobacco-free nicotine pouches (ZYN) 3 mg	Oral mucosal vasculature	61 min	8 ng/mL	Lunell et al., 2020 (92)
Tobacco-free nicotine pouches (ZYN) 6 mg	Oral mucosal vasculature	66 min	15 ng/mL	Lunell et al., 2020 (92)
Tobacco-free nicotine pouches (ZYN) 8 mg	Oral mucosal vasculature	59 min	19 ng/mL	Lunell et al., 2020 (92)
Nasal spray 1 mg	Nasal mucosal vasculature	11–18 min	5–8 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Inhaler 4 mg released (one 10 mg cartridge, 20 min)	Nasal mucosal vasculature	30 min	8 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Oral capsule 3–4 mg	Oral mucosal vasculature	90 min	6–8 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Oral slow-release capsule (colonic absorption) 6 mg	Oral mucosal vasculature	7.5 h	2 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Oral solution 2 mg	Oral mucosal vasculature	51 min	5 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Oral solution ~3 mg	Oral mucosal vasculature	66 min	3 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Enema ~3.5 mg	Anal mucosal vasculature	20–80 min	2–3 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Enema 6 mg	Anal mucosal vasculature	45 min	6–9 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Gum 2 mg	Oral mucosal vasculature	30 min	6–9 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Gum 4 mg	Oral mucosal vasculature	30 min	10–17 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Gum 4.2 mg	Oral mucosal vasculature	45 min	9 ng/mL	Digard et al., 2013 (94) Renard et al., 2025 (93)
Lozenge 2 mg	Oral mucosal vasculature	60 min	4 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Lozenge 4 mg	Oral mucosal vasculature	66 min	11 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Sublingual tablet 2 mg	Oral mucosal vasculature	~60 min	4 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Subcutaneous injection 2.4 mg	Venous capillaries and small veins	25 min	15 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Intravenous injection 5 mg	Venous capillaries and small veins	30 min	30 ng/mL****	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Tooth patch 2 mg	Oral mucosal vasculature	~120 min	3 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Dermal patch 14 mg (Nicoderm)	Venous capillaries and small veins	6–9 h	11–14 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Dermal patch 15 mg (Nicotrol)	Venous capillaries and small veins	4–7 h	11–16 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Dermal patch 21 mg (Nicoderm)	Venous capillaries and small veins	3–7 h	18–23 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Dermal patch 21 mg (Habitrol)	Venous capillaries and small veins	9–12 h	12–21 ng/mL	Benowitz et al., 2009 (86) Hukkanen et al., 2005 (87)
Disposable vapes (Cig-a-likes) – 1^st gen. variable nicotine level	Pulmonary, oral, pharyngeal circulation	6–13 min	4–9 ng/mL	Voos et al., 2019 (98) Hajek et al., 2017 (99)
Disposable vapes – 2^nd gen. variable nicotine level	Pulmonary, oral, pharyngeal circulation	6–10 min	4–12 ng/mL	Voos et al., 2019 (98) Yuki et al., 2017 (100) Hajek et al., 2017 (99)
Juul-type e-cigs 59 mg	Pulmonary, oral, pharyngeal circulation	6 min	11 ng/mL	Goldenson et al., 2021 (101)
Juul-type e-cigs 18 mg	Pulmonary, oral, pharyngeal circulation	6 min	4 ng/mL	Goldenson et al., 2021 (101)
Juul-type e-cigs 9 mg	Pulmonary, oral, pharyngeal circulation	7 min	2 ng/mL	Goldenson et al., 2021 (101)
Vape pen (myblu) nicotine salt 25 mg nicotine	Pulmonary, oral, pharyngeal circulation	6 min	8 ng/mL	Anonymous 2019 (102)
Vape pen (myblu) 25 mg free base nicotine	Pulmonary, oral, pharyngeal circulation	8 min	5 ng/mL	Anonymous 2019 (102)
Box mods	Pulmonary, oral, pharyngeal circulation	10 min	7 ng/mL	Voos et al., 2019 (98)
Sub-ohm devices	Pulmonary, oral, pharyngeal circulation	72 min	13 ng/mL	St Helen et al., 2016 (103)
Sub-ohm devices	Pulmonary, oral, pharyngeal circulation	65 min	23 ng/mL	Farsalinos et al., 2014 (104)
E-pipe	Pulmonary, oral, pharyngeal circulation	10 min	5 ng/mL	Voos et al., 2019 (98)
E-cigar	Pulmonary, oral, pharyngeal circulation	10 min	3 ng/mL	Voos et al., 2019 (98)

[i] Definitions:

[ii] 1^st gen.: low-capacity batteries w/polyfil-filled atomizers (used free base nicotine)

[iii] 2^nd gen.: high voltage output to atomizer w/electric circuits (used free base nicotine)

[iv] 3^rd gen.: (sometimes called “mods”) – larger devices, allows the user to control many features (e.g., device power, heating temperature) and also are refillable. Generally, these devices use e-liquids that have moderate levels of free base nicotine

[v] Sub-ohm devices: large devices, allow the user to control many features (e.g., device power, heating temperature) and are refillable. Generally, these devices use e-liquids that have low levels of free base nicotine.

Table 5.

Inflammation-associated effects of nicotine in human disease.

Disease	Association with smoking or e-cigarettes	Role of nicotine	References
Ulcerative colitis (UC)	Smoking decreases risk and ameliorates symptoms E-cigarettes did not exacerbate UC	Ameliorates pathology and symptoms	Mi et al., 2025 (120) Pullan et al., 1994 (121) Sandborn et al., 1997 (122) Sheehan et al., 2023 (123)
Crohn's disease (CD)	Smoking increases risk and exacerbates pathology E-cigarettes did not exacerbate CD (123) E-cigarettes trended toward increased surgical resection in CD (124)	Probably ameliorates pathology and symptoms (limited data)	Mínguez and Nos, 2024 (3) Ingram et al., 2008 (125) Sheehan et al., 2023 (123) Parigi et al., 2025 (124)
Multiple sclerosis (MS)	Smoking increases the risk and exacerbates symptoms	Nicotine use is not harmful and probably protective.	Rosso and Chitnis, 2020 (126) Hedström et al., 2013 (127) Cleveland Clinic, 2026 (128) Hao et al., 2011 (129) Gao et al., 2014 (130) Jiang et al., 2016 (131) Rothbard et al., 2018 (5)
Pulmonary sarcoidosis	Current smoking reduces risk	Nicotine normalizes immune responses and improves FVC.	Dehara et al., 2025 (132) Julian et al., 2013 (133) Crouser et al., 2021 (134)
Rheumatoid arthritis (RA)	Smoking increases the risk, exacerbates the clinical course, and reduces therapeutic efficacy	Nicotine is probably not associated with RA. Nicotine can dampen inflammation in RA patients. Nicotine replacement used for RA patients.	Tang and Mok, 2025 (135) Ishikawa and Terao, 2020 (136) Carlens et al., 2010 (137) Bruchfeld et al., 2010 (138) Esbensen et al., 2026 (139)
Sepsis	Smoking increases the risk	Nicotine is anti-inflammatory in animal models of sepsis.	Cleveland Clinic, 2026 (140) Lee et al., 2024 (141) Özdemir-Kumral et al., 2017 (142) Wang et al., 2004 (143) Keever et al., 2024 (144)

Table 6.

E-cigarettes and important physical characteristics.

	Disposable e-cigarette	Cig-a-like e-cigarette (1^st generation)	Vape pens (2^nd generation)	Pod mods (2^nd/3^rd generation)	Box mods and tanks (3^rd/4^th generation)	References
Description	Single-use, not rechargeable or refillable, convenient, puff-activated	—	Larger than cig-a-like, cylindrical in shape, rechargeable, usually refillable, better battery life, better vapor production vs. cig-a-like	Compact, rechargeable, uses pre-filled or fillable pods (instead of tanks), often uses nicotine salts	Large, highly customizable, users can change voltage, wattage and temperature, often use sub-ohm tanks for increased vapor production	USDHHS, 2019 (205)
Power (wattage)	7–15 W	7–15 W	10–50 W	10–50 W	10–200 W	Meebaco Products, 2026 (206) Jackson, 2025 (207)
Temperature range (°C)	160–250 °C	160– 250 °C	195–255 °C	157–266 °C	157–266 °C	Cui et al., 2017 (110) Li et al., 2021 (208) Tran et al., 2023 (209) Zhao et al., 2016 (210)
Aerosol mass	7–8 mg/puff	7–8 mg/puff	10–12 mg/puff	10–12 mg/puff	7–22 mg/puff	Lalo et al., 2020 (211) Tran et al., 2023 (209)
Metal risk assessment	These e-cigarettes usually contain high levels of lead and anti-mony from leaching non-heated (like leaded bronze alloys)	Models with heating coils of Nichrome have risks of nickel and chromium	Models with heating coils of Nichrome have risks of nickel and chromium	Generally, show high concentrations of cobalt and nickel compared to other models	Generally, show high concentrations of cobalt and nickel compared to other models	Salazar et al., 2025 (212) Aherrera et al., 2023 (213)

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DOI: https://doi.org/10.2478/cttr-2026-0009 | Journal eISSN: 2719-9509 (formerly 1612-9237)

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Language: English, French, German

Page range: 116 - 147

Submitted on: Mar 9, 2026

Accepted on: Jun 18, 2026

Published on: Aug 31, 2026

Published by: Beiträge zur Tabakforschung GmbH

In partnership with: Paradigm Publishing Services

Keywords:

rheumatoid arthritis,

sepsis,

multiple sclerosis,

pulmonary sarcoidosis

Related subjects:

Life sciences,

Life sciences, other

© 2026 Carr J. Smith, Thomas A. Perfetti, published by Beiträge zur Tabakforschung GmbH
This work is licensed under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0 License.

Volume 35 (2026): Issue 3 (August 2026)

Nicotine Is Not a Proinflammatory Component of E-cigarette Vapor

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Table 2.

Table 3.

Figure 1.

Table 4.

Table 5.

Table 6.

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