Interactions between STAT3 and metabolic enzymes have also been demonstrated previously whereby blockade of PFKFB3 leads to inhibition of pSTAT3 expression in RA FLS [10], and nuclear PKM2 can act as a protein kinase which phosphorylates STAT3 transcription which in turn promotes IL-6 and IL-1β secretion [129]. This evidence concerns the gene IL1B and rheumatoid arthritis.