Applications of C5a antagonists in vivo

许多严重的炎症性疾病，如关节炎、败血性休克、肺休克和心脏病，用现有的药物控制效果很差。有很多证据表明，一种称为补体的循环激素系统与这些疾病的恶化有关，但没有药物可以抵消其影响。补体系统的一个强大的组成部分，称为C5a，引起炎症，并被怀疑引起组织损伤和这些和许多其他免疫疾病的痛苦。一种能够阻断C5a作用的药物在临床上可能非常有用。目前还没有这种药物。我们已经开发了在分离的细胞和组织的实验室测试中特异性阻断C5a的强大试剂，现在提出在模拟上述人类疾病状况的大鼠中测试它们的有效性。我们的初步结果非常有希望，我们将进行进一步的测试，以确定新药的作用范围。我们的一种新药物在大鼠中具有口服活性，我们将确定该药物的血液水平与其有益效果之间的关系。我们还计划开发口服更有效的药物。这些结果可能会导致一种新型的抗炎药物，用于目前治疗效果不佳的各种疾病。

Many serious inflammatory diseases, such as arthritis, septic shock, lung shock and heart disease are poorly controlled with currently available drugs. There is much evidence that a circulating hormone system called complement is involved with exacerbating these diseases, yet there are no drugs available to counteract its effects. One powerful component of the complement system, called C5a, causes inflammation and is suspected of causing tissue damage and suffering in these and many other immune diseases. An agent that could block the effects of C5a could be very useful clinically. There is no such drug available as yet. We have developed powerful agents which specifically block C5a in laboratory tests on isolated cells and tissues, and now propose to test their effectiveness in rats in which the above human disease conditions are mimicked. Our preliminary results are very promising, and we will conduct further testing to determine the scope of the actions of the new drugs. One of our new agents is orally active in rats, and we will determine how the blood levels of the drug relate to its beneficial effects. We are also planning to develop agents that are more effective when given by mouth. The results could lead to a new type of anti-inflammatory drug for humans suffering from a variety of diseases that are poorly treatable at present.