Centre for Mathematical Biology and Ecology, Department of Mathematics, Jadavpur University, Kolkata 700032, India.
Systems Ecology & Ecological Modeling Laboratory, Department of Zoology, Visva-Bharati University, Shantiniketan 731235, India.
J Theor Biol. 2019 Aug 7;474:63-77. doi: 10.1016/j.jtbi.2019.04.007. Epub 2019 Apr 11.
Psoriasis is a chronic skin condition that produces plaques of condensed, scaling skin due to excessively rapid proliferation of keratinocytes. During the disease progression, keratinocyte proliferation is influenced by many immune cells and cytokines. This article deals with a five dimensional deterministic model, which has been derived using quasi-steady-state approximation for describing the dynamics of psoriasis in various cytokines environment. Equilibrium analysis of the system shows that either the system converges to a stable steady state or exhibits a periodic oscillation depending upon system parameters. Finally, introducing a one dimensional impulsive system, we have determined the perfect dose and perfect dosing interval for biologic (TNF-α inhibitor) therapy to control the hyper-proliferation of keratinocytes. We have studied the effect of TNF-α inhibitor by considering both perfect and imperfect dosing during the inductive phase. The maximum possible number of drug holidays and the minimal number of doses that must subsequently be taken while avoiding drug resistance have been calculated for imperfect dosing. Since, psoriasis is non-curable but treatable disease, so the aim is to investigate the minimum dose with highest efficacy and proper dosing interval of TNF-α inhibitor for a psoriatic patient. Through numerical simulations, we have given a detailed prediction about the maximum drug holidays, tolerable for a patient, without loss of previous drug effects. Our theoretical predictions and numerical outcomes may be useful in guiding the design of future clinical trials.
银屑病是一种慢性皮肤疾病,由于角质形成细胞过度快速增殖而产生致密的鳞屑斑块。在疾病进展过程中,角质形成细胞的增殖受到许多免疫细胞和细胞因子的影响。本文涉及一个五维确定性模型,该模型是使用准稳态近似法推导出来的,用于描述各种细胞因子环境下银屑病的动力学。系统的平衡分析表明,系统要么收敛到稳定的稳态,要么根据系统参数表现出周期性振荡。最后,引入一维脉冲系统,我们确定了生物(TNF-α 抑制剂)疗法的最佳剂量和最佳给药间隔,以控制角质形成细胞的过度增殖。我们在诱导期考虑了完美和不完美的给药,研究了 TNF-α 抑制剂的作用。计算了不完美给药时最大可能的药物假期次数和随后避免耐药性所需的最小剂量。由于银屑病是一种不可治愈但可治疗的疾病,因此目的是为银屑病患者研究 TNF-α 抑制剂的最低有效剂量和最佳给药间隔。通过数值模拟,我们对患者可承受的最大药物假期进行了详细预测,而不会失去先前的药物效果。我们的理论预测和数值结果可能有助于指导未来临床试验的设计。