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Nicotine Treatment For Ulcerative Colitis

1 2
Saraswita Gabrillah Saetikho , Banun Kusumawardani
1
S1 Student, Faculty of Dentistry, Jember University, Jember, Indonesia
2
Correspondence, Doctor in Jember University, Laboratorium of Oral Pathology, Department
of Biomedical Sciences, Faculty of Dentistry, Jember University, Jember, Indonesia

Abstract
Introduction: Ulcerative colitis (KU) disease is a chronic inflammatory disease of colon
especially regarding the part of the colonic mucosa. This disease is one of inflammatory bowel
diseases (IBD). Discussion: Nicotine was found to suppress the function of Th2 in vivo cells as
measured by inhibition of interleukin-10 production, and to reduce the synthesis of interleukin-2
and interleukin-8 by mononuclear cells. Recent data indicate that flare-up of ulcerative colitis often
occurs earlier in steroid-treated patients than with nicotine patch treatments. Conclusions:
Transdermal nicotine alone has limited efficacy for active ulcerative colitis and is not as effective
as treatment. But when given in combination with mesalamine, more efficacious alternative
nicotine are effective and provide a therapeutic effect longer than prednisone.

Keywords: Ulcerative colitis, Colon, Inflammatory bowel diseases, Nicotine.

Keywords
Ulcerative colitis, Colon, Inflammatory bowel diseases, Nicotine.

INTRODUCTION
Ulcerative colitis is a chronic inflammatory disease of the colon, especially concerning the
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mucosal part of the colon. This disease is one of the inflammatory bowel diseases (IBD),
which until now has not known the cause clearly The cause of IBD is still unclear, but
related to genetic factors and environmental factors as a trigger this is evident from 10-
20% of patients must have family members affected by the same disease. Ulcerative colitis
includes autoimmune diseases related to the inflammatory response of bacteria in the
colon. Broadly speaking IBD consists of 3 types, namely ulcerative colitis, Crohn's
disease, and if it is difficult to distinguish between the two, it is included in the category of
indeterminate colitis Ulcerative colitis is one of two types of Inflammatory Bowel Disease,
in addition to Crohn disease (Guslandi,1999).

People who do not smoke have a great potential with Collis ulcerative disease compared to
smokers.

Corresponding author: Electra D. Paskett, PhD, The Ohio State University, 1590 North High Street, Suite 525, Columbus, OH 43201;
(614) 293-3917, phone; (614) 293-5611, fax;
Electra.Paskett@osumc.edu. Disclosures: The authors report no conflicts
of interest
 This is because toxins called Nitric Oxide in Nicotine can reduce the activity of circular
muscle activity, the release of nitrate in the intestinal wall can also ward off inflammatory
bowel disease. (Guslandi,1999)
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THEORY
Ulcerative colitis is a chronic inflammation of colon that causes ulceration. Ulceration and
inflammation of the lining of the colon causes symptoms of abdominal pain, diarrhea, and rectal
bleeding. This condition is associated with intestinal inflammation called Crohn's
disease(Guslandi,1999).Ulcerative colitis and Crohn's disease are chronic conditions that can last
for years to decades, beginning during adolescence and early adulthood or childhood.
Inflammation in the colon also causes the bowel is often empty, causing diarrhea. Ulcerative
colitis is an inflammatory bowel disease (Jugde,2003)Tobacco chemical content that has been
identified amounted to 2,500 components. 1,400 others decomposed or split, acting with other
components and forming new components and forming new components all of which form
approximately 4,800 chemical components in the smoke. In tobacco chemical content included
(Susilowati,2006).
1. Nitrogen compounds (nicotine, protein).
Nicotine (-pyridyl--N-methyl pyrrolidine) is a specific organic compound contained in tobacco
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leaves. Nitric Oxide in nicotine can reduce the activity of circular muscle activity, the release of
nitrates in the intestinal wall can also ward off inflammatory bowel disease. Protein makes the
flavor very intense and biting, so during the processing (curing) this compound should be
overhauled into other senayawa such as amides and amino acids.
2. Carbohydrate compounds (starch, pectin, cellulose, sugar).
Starch, pectin, and cellulose are high-powered compounds that harm the aroma and taste of
suction, so that during the processing must be overhauled into sugar. Sugar has a role in relieving
heavy feeling in cigarette butts if too high causes heat and esophageal irritation, and causes
tobacco to absorb moisture (moisture) so damp.
3. Resins and essential oils.
Leaf sap that is in the hairs of leaves contains resin and essential oils, in the burning will cause a
fragrant smell of cigarette smoke. Tobacco also has active ingredients as anti-bacteria and fungi
among other classes of phenol in the form of flavonoids, alkanoid groups of nicotine, saponins in
the form of steroids as well as atsiri form of terpenoid oil.
n spite of extensive investigation, the exact mechanisms involved in the therapeutic effects of
nicotine in ulcerative colitis remain elusive. It has been reported that nicotine increases the
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thickness of colonic mucus, thus enhancing the protection of the intestinal mucosa. It has been
suggested that nicotine influences the cellular and the humoral immune system and interferes
with the inflammatory response, perhaps through stimulation of endogenous steroid release
Indeed nicotine has been found to suppress in vivo Th2 cell function as measured by inhibition of
interleukin-10 production , and to reduce the synthesis of interleukin-2 and interleukin-8 by
mononuclear cells (Bhatti,1997)

DISSCUSION

Ulcerative colitis is largely a non-smoker disease, and it has been suggested that transdermal
nicotine can be a therapeutic value in active disease. Due to the many common side effects, we
developed a nicotine formulation as a therapeutic agent for ulcerative colitis. Much
epidemiological evidence that smoking protects against ulcerative colitis, The risk of developing
disease is significantly lower in smokers than non-smokers or ex-smokers. Patients with
ulcerative colitis who start smoking often have clinical elevations encouraging attempts to verify
the hypothesis that nicotine may be an active component. Initial and uncontrolled observations
using nicotine gum, a pharmaceutical form that is usually not well-tolerated, produces good but
 i rials, 16 patients with left-sided colitis who received various types of therapy (mesalazine,
n sulphasalazine, steroids) and given 30 mg of nicotine daily were given transdermal fillings for 4
c weeks. The majority of patients report clinical, endoscopic and histologic improvement during
o nicotine administration (Guslandi, 1999).
n
c A multicentre, double blind, placebo-controlled trial conducted in the UK was demonstrated in
l patients with ulcerative colitis who had applied transdermal nicotine (15-25 mg daily for 6
u weeks) in addition to continuous therapy (oral mesalazine or corticosteroids). superior in terms of
s clinical and histological improvement. Similar results have been reported by multicentre
i controlled trials conducted in the United States, where in 4 weeks 39% of patients receiving
v transdermal nicotine reported clinical improvement - as assessed by the 13-point disease activity
e index measuring stool frequency, rectal bleeding, endoscopic findings and clinical global
evaluation - compared with 9% of patients receiving placebo (Guslandi, 1999).
r
e In a controlled study, patients who experienced acute ulcerative colitis flare-ups during
s maintenance treatments with mesalazine were given additional treatment with transdermal
u nicotine 15 mg daily or prednisone for 5 weeks and then followed for 6 months while
l continuously being given mesalazine. ulcerative colitis was observed in 20% of nicotine-treated
t patients and in 60% of patients in the prednisone group (P = 0.027) People treated with patches
s of nicotine recurred earlier in people successfully treated with steroids, concluded from this data
. that transdermal nicotine alone have limited efficacy in active and ineffective ulcerative colitis as
maintenance treatments. On the other hand, if given in combination with mesalazine, nicotine is
I superior to placebo, it has been reported that nicotine increases the thickness of the colonic
n mucus, thus improving intestinal mucosal protection. Nicotine affects the cellular and humoral
immune systems and interferes with the inflammatory response, through stimulation of
o endogenous steroid release. Nicotine was found to suppress the function of Th2 in vivo cells as
p measured by inhibition of interleukin-10 production, and to reduce the synthesis of interleukin-2
e and interleukin-8 by mononuclear cells. Nitric Oxide in nicotine can also stimulate colonic
n mucus and inhibition of inflammatory cytokines play a role in reducing circular muscle activity,
the release of nitrates in the intestinal wall can also counteract colitis (Guslandi, 1999).
t

CONCLUSION
Ulcerative colitis is a disease more commonly seen in non-smokers or former smokers. In mild to
moderate cases, the addition of transdermal nicotine to conventional therapy (usually mesalazine)
for 4-6 weeks results in clinical improvement and may also be a therapeutic alternative when
corticosteroids are unusable. Overall, the therapeutic effect of nicotine is consistent. Nicotine was
found to suppress the function of Th2 in vivo cells as measured by inhibition of interleukin-10
production, and to reduce the synthesis of interleukin-2 and interleukin-8 by mononuclear cells.
transdermal nicotine alone has limited efficacy for active ulcerative colitis and is not as effective
as treatment. But when administered in combination with mesalazine, nicotine is more efficacious
and works a longer therapeutic effect than prednisone.
.

Acknowledgments

Firstly, I would like to express my sincere gratitude to my advisor Dr. drg. Banun Kusumawardani,
M. Kes. for the continuous support of my study, for her patience, motivation, and immense
knowledge. Her guidance helped me in all the time of writing of this Article. I could not have
imagined having a better advisor and mentor for my study.
 References
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1. Guslandi M, Tittobello A.1999.Nicotine treatment for ulcerative colitis.48(4):

481484.
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2. Kuhbacher T, Folsch UR. 2007 Practical guidelines for the treatment of in

ammator bowel disease. World J Gastroenterol; 13(8): 1149 55.

3. Bhatti MA, Hodgson I. Inflammatory bowel disease IL-8 production and

tissue expression Is modulated by nicotine and crude tobacco extract.
Gut. 1997;40(Suppl 1):A74.

4. Susilowati, E. Y. 2006. Identifikasi nikotin dari Daun Tembakau kering dan

Uji Efektifitas Ekstrak Daun tembakau. Semarang : Universitas Negeri
semarang

5. Cottone M, Rosselli M, Orlando A, et al. Smoking habits and recurrence in

Crohns disease. Gastroenterology. 1994;106:643648.

6. Jugde TA. Inflammatory Bowel Disease. In: Friedman SL, McQuaid

KR, Grendell JH, 2003. Current Diagnosis and Treatment in
Gastroenterology. 2nd ed. International ed.: McGraw-Hill; p. 108-30.

7. Thomas GO, Rhodes J, Green JT. Inflammatory bowel disease and smoking
a review. Am J Gastroenterol. 1998;93:144149.

8. Lashner BA, Hanauer SB, Silverstein MD. Testing nicotine gum for ulcerative
colitis patients. Experience with single-patient trials. Dig Dis Sci. 1990;35:827
832.

9. Sandborn WJ, Tremaine WJ, Offord KP, et al. Transdermal nicotine for mildly
to moderately active ulcerative colitis. A randomized, double-blind, placebo-
controlled trial. Ann Intern Med. 1997;126:364371.

10. Zijistra FJ, Srivastava ED, Rhodes M, et al. Effect of nicotine on rectal mucosa and mucosal
eicosanoids. Gut. 1994;35:247251.