Indeed, human neutrophils produced IL-8 in response to rPVL independently of IL-1 signaling. Furthermore, IL-8 levels were strongly reduced in neutropenic rabbits. ii) S. aureus and leukocidins/PSMs-intoxicated neutrophils release numerous proteases, which might degrade/inactivate Kineret/IL-1Ra. iii) Endogenous IL-1Ra, which is up-regulated during bacterial pneumonia, might mask the action of exogenously added IL-1Ra/Kineret. In our sterile pneumonia model, despite the efficient block of IL-1 signaling and a reduction of 50% in IL-8 level, we found no reduction in ICI 63197 neutrophil infiltration into the lung. This result suggests that neutrophil recruitment in the lung is based on several redundant pathways and would require the targeting of numerous signaling pathways to be significantly reduced. Similarly, the failure of Kineret/IL-1ra clinical trials in severe sepsis led to the conclusion that strategies aimed at targeting a single inflammatory mediator were unlikely to work in such complex diseases. Importantly, such a lesson can be learned from S. aureus, which has evolved a large number of virulence factors targeting neutrophils. Endosseous implants are widely used for the restoration of edentulism with long-term success rates often exceeding 90%. This is one of the most successful treatment modalities in the field, and has significantly improved the patients�� quality of life. In order to further improve treatment success rate, different levels of modifications of implants have been emphasized. Among those, surface modification has been extensively investigated provided that it is the first component to interact with the host. For instance, the so-called moderately micro roughened surface, with the arithmetic average height deviation of approximately 1.5 mm, was shown to present Spermine NONOate enhanced bone response relative to turned or excessively roughened surfaces. Recent research has suggested that the presence of nanotopography may be one of the decisive factors for early osseointegration. Surface modification at the nanolevel was shown to increase the bioactivity of the implant surface, which resulted in significant enhancement of new bone formation in vivo. Of great interest was the fact that the nanotextured surfaces not only enhanced the bone formation but also strengthened the biomechanical properties. Also of relevance are nanochemical alterations involving hydroxyapatite or other calcium phosphate compositions.