Most cytokines were detected at very low levels before and after high-dose chemotherapy, and although changes were statistically significant, the biological relevance remains unclear. The BioRad research department uses a set of cytokine values they consider as ‘normal’. However, these values have not been

validated. Only our IL-5, IL-6 and INFγ results have values higher than the ‘normal’ BioRad values (Professor Tor Lea, University of Life Science, Norway, personal communication), which suggests that only these three cytokines reflect clinical significant differences. The complement system was slightly activated in this population PF-02341066 clinical trial of neutropenic lymphoma patients as revealed by a significant increase in both C3bc, an early marker of activation, and TCC, a late marker of activation. The complement activation we found histone deacetylase activity might contribute to a low-grade, probably sterile, inflammatory response. Activation is far greater in some patients with non-neutropenic severe bacterial infection [21]. Constitutively low MBL levels have been associated with a more severe course of febrile neutropenia [8–13, 22]. In contrast to this, we did not find that low MBL values affected the clinical course in our patients. However,

our patients with decreased MBL levels did not develop bacteriaemia. Collectively, our data do not support any role for MBL in febrile neutropenia in a patient population with modest clinical symptoms. The tobramycin once-daily group

had peak tobramycin concentrations generally three times higher than those who received tobramycin three times daily, even though the total tobramycin doses were the same. Comparing the immune responses in patients receiving tobramycin once versus three times daily (Table 3), we found significantly higher increases in several of the proinflammatory cytokines in the patients receiving tobramycin once daily. This has not previously been described [17, 23]. Tobramycin has been associated with increased release from polymorphonuclear leucocytes (PMN) of the proinflammatory cytokines IL-1β, IL-6, IL-8 and TNFα, but not during the anti-inflammatory IL-10 [22]. The highest levels have been observed for IL-6 [23]. We found increases in IL-1b, IL-4, IL-6, IL-7, IL-8, G-CSF, GM-CSF, INFγ and TNFα (Table 2), results that are in accordance with the previous findings [23]. However, these previous findings have not been associated with different tobramycin concentrations. Our patients were neutropenic, abating a possible PMN-mediated response to tobramycin, but our data still indicate that the higher peak concentrations following once-daily dosing have caused a stronger proinflammatory response. This most likely reflects production of these cytokines by other immune cells, such as T-lymphocytes.