1. Advanced Biomedical Research | 2015 1
Letter to Editor
asthma and other allergic diseases. Rolipram, being
an investigational drug, should be combined with
salbutamol and corticosteroids for the management of
asthma. In addition, specific eotaxin inhibitors need
to be identified that may not only help us to rectify
asthmatic problems, but also leads to avoidance of
asthmatic exacerbations and most other infections
leading to eosinophilia.
Hamza Hassan Khan, Salman Assad,
Muhammad Aadil Rahman, Asfandyar Khan Niazi
Shifa College of Medicine, Shifa Tameer‑e‑Millat University,
Islamabad, Pakistan
Address for correspondence: Dr. Hamza Hassan Khan,
Shifa College of Medicine, Shifa Tameer‑e‑Millat
University, Islamabad, Pakistan.
E‑mail: humzahassankhan@hotmail.com
REFERENCES
1. Milara J, Navarro A, Almudéver P, Lluch J, Morcillo EJ, Cortijo J. Oxidative
stress‑induced glucocorticoid resistance is prevented by dual PDE3/PDE4
inhibition in human alveolar macrophages. Clin ExpAllergy 2011;41:535‑46.
2. BinMahfouz H, Borthakur B, Yan D, George T, Giembycz MA, Newton R.
Superiority of combined phosphodiesterase PDE3/PDE4 inhibition over
PDE4 inhibition alone on glucocorticoid‑ and long‑acting β2‑adrenoceptor
agonist‑induced gene expression in human airway epithelial cells. Mol
Pharmacol 2015;87:64‑76.
3. Lucarini L, Pini A, Gerace E, Pellicciari R, Masini E, Moroni F.
Poly (ADP‑ribose) polymerase inhibition with HYDAMTIQ reduces
allergen‑induced asthma‑like reaction, bronchial hyper‑reactivity and airway
remodelling. J Cell Mol Med 2014;18:468‑79.
4. Patel BS, Prabhala P, Oliver BG, Ammit AJ. Inhibitors of PDE4, but
Not PDE3, Increase ß₂‑agonist‑induced Expression of
Anti‑inflammatory MKP‑1 inAirway Smooth Muscle Cells.Am J Respir Cell
Mol Biol 2014; ISN1535‑4989; DOI: 10.1165.
5. Abbott‑Banner KH, Page CP. Dual PDE3/4 and PDE4 inhibitors: Novel
treatments for COPD and other inflammatory airway diseases. Basic Clin
Pharmacol Toxicol 2014;114:365‑76.
Sir,
I am writing this letter to comment on several
previously published articles on the use of
phosphodiesterase (PDE) 3 in combination with PDE
4 in patients with bronchial hyper‑reactivity.[1,2]
These
articles suggest the superiority of this combination
over conventional treatment; however, as discussed
later, rolipram, an investigational PDE 4 inhibitor,
may comparatively prove to be more beneficial
when used in combination with a beta‑agonist and
corticosteroids.
Bronchial hyper‑reactivity responses involve
bronchial inflammation characterized by activation
and accumulation of dendritic cells, eosinophils,
mast cells, macrophages, T‑lymphocytes, and tissue
remodeling process.[3]
Eotaxin, a chemo‑attractant,
causes up regulation of CD11b, eosinophil
accumulation during an allergic response in lungs,
and shedding of L‑selectin in human eosinophils.
Rolipram inhibits CD11b up regulations as well
as eotaxin‑induced trans‑endothelial movement
of eosinophils causing inhibition of eosinophil
recruitment. In addition, rolipram also inhibit tumor
necrosis factor (TNF)‑alpha, at both mRNA and
protein levels, thus enhancing its anti‑inflammatory
effects.[4]
Moreover, Since PDE 4 enzymes are widely
present in the respiratory tract that makes them
susceptible to their inhibition by local application
therefore inhaled administration of PDE 4 inhibitor
has shown considerably more improvement.[5]
On
the other hand, beta‑agonist cause bronchodilation
therefore the synergistic effect of beta‑agonist
with PDE 4 inhibitor is indicated by inhibition
of antigen‑induced contraction and reduction of
increase in vascular permeability which are key
factors responsible for the patho‑physiology of allergic
diseases like asthma.[4]
Furthermore, corticosteroids
such as dexamethasone and fluticasone also partially
reduce the release of eotaxin.
The combined use of β2
‑agonists, rolipram, and steroids
abolished TNF‑α‑induced eotaxin release and hence
their combination has additive beneficial effects in
the treatment of the eosinophilia associated with
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DOI:
10.4103/2277-9175.166647
Rolipram: Eotaxin and phosphodiesterase IV inhibitor versus
bronchial hyper‑reactivity response
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