It is surprising that TNFα did not show cytokine-specific regulation of protein spots because it is an important stimulator for the NF-κB pathway, regulating multiple inflammatory mediators that are not regulated by GM-CSF [ 21].
Persistent pain caused by CFA intraplantar injection involves central sensitization due to the release of multiple inflammatory and pain mediators that account for sensitivity increase of both peripheral sensory afferents at the injury site, and in the central nervous system [ 19, 30].
Bone resorption is tightly and dynamically regulated by multiple mediators, including cytokines that act directly on osteoclasts and their precursors, or indirectly by modulating osteoblast lineage cells that in turn regulate osteoclast differentiation.
However, although Avastin confers a survival benefit to patients with colon, lung and kidney cancer when used in combination with chemotherapy (Hurwitz et al, 2004), this agent is rarely curative, as tumours often secrete multiple mediators of angiogenesis that compensate for the loss of VEGF-A activity.
The airway epithelium plays a significant role in the pathology of allergic asthma, since these cells serve as a source of multiple cytokines, chemokines, growth factors and other mediators that contribute to the immune response against inhaled allergens [26], [27].
GBS cell wall preparations and culture supernatants can activate macrophage/monocytes through multiple Toll-like receptors, leading to the release of abundant cytokines and other proinflammatory mediators that contribute to cell and organ dysfunction during sepsis [6], [14] [16].
No single event or factor has been clearly implicated as being responsible; it is more likely that multiple mediators act at various times throughout the course of the condition.
We ran two mediation analyses: (1) single mediation models (unadjusted, a model that has single mediator), (2) multiple mediation model (adjusted, to obtain the significance of individual mediators within the context of a model that has multiple mediators simultaneously and account for the biological direction between mediators).
We have shown that extending the mediation framework to multiple mediators gives rise to complexities (in terms of multiplicity of definitions) and challenges (for identification) beyond what might have been anticipated.
In the absence of multiple mediators of immunity, we hypothesized that the role of neutrophils during influenza virus infection could be studied more effectively.
