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The paper in this issue of British Journal of Pharmacology, TNF-a-induces airway hyperresponsiveness to cholinergic stimulation in guinea pig airways, by Makwana et.al from Sackler Institute of Pulmonary Pharmacology presents the role of TNF-alpha in triggering bronchoconstriction and cholinergic airway resistance associated with asthma and the effects of utilising different agonists and antagonists such as acetylcholine, atropine, hexamethonium and ketanserin in stimulate contraction of tracheal ring tissue. TNF-alpha is an agent which contains cytokine that causes the diseases of airway inflammation, asthma, bronchoconstriction and also airway hyperresponsiveness (Cockcroft et al, 2006; Jaymin B et.al, 2006). This new studies significantly shows that the responses of methacholine, 5-HT and EFS to tracheal contraction before adding and after cytokines are similar which shows not much noteworthy different between freshly prepared and saline-incubated condition. Furthermore, their studies further extend in airway hyperresponsiveness and bronchospasm. 5-HT is defined as 5-hydroxytryptamine and it is an inflammatory lipid mediators which acts as an agonist that enhance muscle contraction (Hoyer et.al, 2002). Detailed analysis of different kinds of stimulation response on contraction of the tracheal segments with the presence or absence of TNF-alpha also identified that TNF-alpha disturb the smoothness and also the inflammation of the airways. These are complex studies, as too much different drug adding in the same tracheal tissue will probably affect the nerve and contractility responses of the tissue so a stable baseline needed to maintain. This article is beneficial to the reader by providing new knowledge on the role of TNF-alpha acting on respiratory pathway so that it can improve the area of understanding the role of TNF-alpha other than in the brain dysfunction such as Parkinson disease, Alzheimer disease and trauma as the research paper mentioned by Ian A. Clark et.al. As the previous studies prepared by Ana Lúcia Borges Shimada et.al already mentioned that exposure of Hydroquinone (HQ), which is one of the agents that can be found in the cigarette smoke will indirectly influence airway contraction through the parasympathetic system which mediated by the TNF-alpha and it already show the relationship between the HQ and TNF-alpha in tracheal hyperresponsiveness. However, this study more highlighted on the relationship between TNF-alpha and the responses of methacholine, 5-HT and EFS which makes reader to more understanding the others possible potency of TNF-alpha other than influence HQ.
This research paper presented the studies by using two different types experimental methods; vitro organ bath and a vivo lung function studies. In vitro organ bath studies, the fresh tracheal ring was incubated in the saline environment which acts as the control of the experiment and also environments with varies amounts of TNF-alpha for 1,2 and 4 days. The tracheal ring was exposure to the MCh, washed out and the amplitude of the contraction was measured by using EFS which known as electrical field stimulation that response to the presence of TNF-alpha by changing the amplitude of the waves.
From the table 1 provided by the authors, it can be seen that the contraction of fresh tracheal rings of the guinea pig when TNF-alpha is added, the frequency of the EFS and the response of 5-HT on tracheal contraction to increase as in the day 4, the contractions to EFS were changing from 23.2 ± 4.7, 45.8 ± 2.9 and 58.3 ± 3.9% and the contractions to 5-HT were increase in trend of 45.2 ± 3.8, 64.1 ± 2.9 and 75.3 ± 2.3% when 1, 10 and 100 ng·mL-1 TNF-a was applied compare to the condition without TNF-alpha which is under saline-treated control. However, R. Makwana report their studies that there is no differences in the methacholine (MCh) results between the before adding and after adding TNF-alpha. Thus, it can be concluded that EFS and 5-HT receptors are sensitive to TNF-alpha but not to the methacholine also TNF-alpha is an essential stimulant that induces airway hyperesponsiveness.
Role of 5-HT as an agonist was strongly supported by the authors by showing a sigmoid curve shape in the concentration-response curves. The higher the concentration of 5-HT added, the greater the impulse generated by the contracting muscle. This article provides interesting data on the relationship between the contraction and methacholine (MCh) by noting performances of methacholine to the muscle contraction will not be affected by the quantity of TNF-alpha added. The maximal contraction still can be achieved even if the tracheal ring is incubated for zero amount of TNF-alpha.
In fact, there are a host of papers demonstrating the addition of atropine in tracheal muscle tissue will still achieve the maximal response. A competitive antagonism was shown in this research paper. It can be elucidated that Atropine is the antagonist of the Ach which reduced the potency of the Ach drug by competing binding to the receptor but this problem can be overcome by increasing the concentration of Ach. Nevertheless, the actual function of ketanserin is still unknown as it only abolished constriction in the presence of 5-HT since there is no data shown.
In vivo lung function studies, the purpose of the author is to examine the effects of air flow resistant of lung, heart rate and the man of arterial blood pressure after added TNF-alpha on the lung of anaesthetized guinea pig. The authors provide convincing evidence for TNF-alpha induce airway resistance by presenting treatment of 5-HT and MCh all increase the lung resistance percentage however only vagal nerves stimulation and 5-HT show great discrepancy results when TNF-alpha is existence.
Therefore, although the article written by R. Makwana et.al on understanding on effects of TNF-alpha on airway hyperresponsiveness is not complete but it significantly enhancing our knowledge data on the relationship of TNF-alpha between electric field stimulation in vivo and contractility in vitro by given convincing with clear description graphs. They also give out suggestions of how a pre-synaptic action of TNF-alpha should be stimulated on parasympathetic nerves and 5-HT2A receptor-mediated acetylcholine release from epithelial cells will increase by introducing TNF-alpha to improve their research studies.